Showing papers in "Pain in 1992"

An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat.

Abstract: SummaryWe attempted to develop an experimental animal model for peripheral neuropathic pain Under sodium pentobarbital anesthesia, both the L5 and L6 spinal nerves (group 1) or the L5 spinal nerve alone (group 2) of one side of the rat were tightly ligated For comparison, a parallel study was cond

Grading the severity of chronic pain.

Abstract: This research develops and evaluates a simple method of grading the severity of chronic pain for use in general population surveys and studies of primary care pain patients Measures of pain intensity, disability, persistence and recency of onset were tested for their ability to grade chronic pain severity in a longitudinal study of primary care back pain (n = 1213), headache (n = 779) and temporomandibular disorder pain (n = 397) patients A Guttman scale analysis showed that pain intensity and disability measures formed a reliable hierarchical scale Pain intensity measures appeared to scale the lower range of global severity while disability measures appeared to scale the upper range of global severity Recency of onset and days in pain in the prior 6 months did not scale with pain intensity or disability Using simple scoring rules, pain severity was graded into 4 hierarchical classes: Grade I, low disability--low intensity; Grade II, low disability--high intensity; Grade III, high disability--moderately limiting; and Grade IV, high disability--severely limiting For each pain site, Chronic Pain Grade measured at baseline showed a highly statistically significant and monotonically increasing relationship with unemployment rate, pain-related functional limitations, depression, fair to poor self-rated health, frequent use of opioid analgesics, and frequent pain-related doctor visits both at baseline and at 1-year follow-up Days in Pain was related to these variables, but not as strongly as Chronic Pain Grade Recent onset cases (first onset within the prior 3 months) did not show differences in psychological and behavioral dysfunction when compared to persons with less recent onset Using longitudinal data from a population-based study (n = 803), Chronic Pain Grade at baseline predicted the presence of pain in the prior 2 weeks Chronic Pain Grade and pain-related functional limitations at 3-year follow-up Grading chronic pain as a function of pain intensity and pain-related disability may be useful when a brief ordinal measure of global pain severity is required Pain persistence, measured by days in pain in a fixed time period, provides useful additional information

The formalin test: an evaluation of the method.

Abstract: The formalin test for nociception, which is predominantly used with rats and mice, involves moderate, continuous pain generated by injured tissue. In this way it differs from most traditional tests of nociception which rely upon brief stimuli of threshold intensity. In this article we describe the main features of the formalin test, including the characteristics of the stimulus and how changes in nociceptive behaviour may be measured and interpreted. The response to formalin shows an early and a late phase. The early phase seems to be caused predominantly by C-fibre activation due to the peripheral stimulus, while the late phase appears to be dependent on the combination of an inflammatory reaction in the peripheral tissue and functional changes in the dorsal horn of the spinal cord. These functional changes seem to be initiated by the C-fibre barrage during the early phase. In mice, the behavioural response in the late phase depends on the ambient temperature. We argue that the peripheral tissue temperature as well as other factors influencing the peripheral inflammation may affect the response, possibly confounding the results obtained with the test. Furthermore, we discuss the methods of recording the response and the value of observing more than one aspect of behaviour. Scoring of several behavioural variables provides a means of assessing motor or sensorimotor function as possible causes for changes in behaviour. In conclusion, the formalin test is a valuable addition to the battery of methods available to study nociception.

Efficacy of multidisciplinary pain treatment centers: a meta-analytic review.

Abstract: Sixty-five studies that evaluated the efficacy of multidisciplinary treatments for chronic back pain were included in a meta-analysis. Within- and between-group effect sizes revealed that multidisciplinary treatments for chronic pain are superior to no treatment, waiting list, as well as single-discipline treatments such as medical treatment or physical therapy. Moreover, the effects appeared to be stable over time. The beneficial effects of multidisciplinary treatment were not limited to improvements in pain, mood and interference but also extended to behavioral variables such as return to work or use of the health care system. These results tend to support the efficacy of multidisciplinary pain treatment; however, these results must be interpreted cautiously as the quality of the study designs and study descriptions is marginal. Suggestions for improvement in research designs as well as appropriate reports of research completed are provided.

The Pain Anxiety Symptoms Scale: development and validation of a scale to measure fear of pain.

Abstract: Fear of pain has been implicated in the development and maintenance of chronic pain behavior. Consistent with conceptualizations of anxiety as occurring within three response modes, this paper introduces an instrument to measure fear of pain across cognitive, overt behavioral, and physiological domains. The Pain Anxiety Symptoms Scale (PASS) was administered to 104 consecutive referrals to a multidisciplinary pain clinic. The alpha coefficients were 0.94 for the total scale and ranged from 0.81 to 0.89 for the subscales. Validity was supported by significant correlations with measures of anxiety and disability. Regression analyses controlling for measures of emotional distress and pain showed that the PASS made a significant and unique contribution to the prediction of disability and interference due to pain. Evidence presented here supports the potential utility of the PASS in the continued study of fear of pain and its contribution to the development and maintenance of pain behaviors. Factor analysis and behavioral validation studies are in progress.

Painful neuropathy: altered central processing maintained dynamically by peripheral input.

Abstract: We performed sensory assessments before and during diagnostic tourniquet-cuff and local anesthetic blocks in 4 patients diagnosed with reflex sympathetic dystrophy (RSD). All patients complained of mechano-allodynia; lightly touching the skin evoked an intense pain sensation. At detection levels, electrical stimuli were perceived as painful, suggesting that the mechano-allodynia was mediated by A beta low-threshold mechanoreceptor afferents. A beta-mediated allodynia was further supported by reaction time latencies to painful electrical stimuli at threshold for A-fiber activation and, in 1 patient, by differential cuff blocks which abolished A beta function and allodynia while thermal sensation (warm and cold) were preserved. Local anesthetic block of painful foci associated with previous trauma abolished mechano-allodynia, cold allodynia, and spontaneous pain in all patients and relieved the motor symptoms in 1 patient with tonic contractures of the toes. Tactile and thermal perception in the previously allodynic area was preserved. When the local anesthetic block waned, spontaneous pain, allodynia, and motor symptoms returned. We propose a model of neuropathic pain in which ongoing nociceptive afferent input from a peripheral focus dynamically maintains altered central processing that accounts for allodynia, spontaneous pain, and other sensory and motor abnormalities. Blocking the peripheral input causes the central processing to revert to normal, abolishing the symptoms for the duration of the block. The model accounts for sympathetically maintained (SMP) and sympathetically independent (SIP) pain. The peripheral input can be independent of sympathetic activity or driven completely or in part by activity in sympathetic efferents or by circulating catecholamines. The shared final common pathway may explain the common features of SMP and SIP.

The consistency of facial expressions of pain: a comparison across modalities

Abstract: A number of facial actions have been found to be associated with pain. However, the consistency with which these actions occur during pain of different types has not been examined. This paper focuses on the consistency of facial expressions during pain induced by several modalities of nociceptive stimulation. Forty-one subjects were exposed to pain induced by electric shock, cold, pressure and ischemia. Facial actions during painful and pain-free periods were measured with the Facial Action Coding System. Four actions showed evidence of a consistent association with pain, increasing in likelihood, intensity or duration across all modalities: brow lowering, tightening and closing of the eye lids and nose wrinkling/upper lip raising. Factor analyses suggested that the facial actions reflected a general factor with a reasonably consistent pattern across modalities which could be combined into a sensitive single measure of pain expression. The findings suggest that the 4 actions identified carry the bulk of facial information about pain. They also provide evidence for the existence of a universal facial expression of pain. Implications of the findings for the measurement of pain expression are discussed.

Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo-controlled studies.

Abstract: For 39 controlled studies on the analgesic effect of antidepressants, a meta-analysis was conducted to get an estimation of the effect size, and to obtain a sight on the possible modes of action and the methodology used. The mean size of the analgesic effect was 0.64. It means that the average chronic pain patient who received an antidepressant treatment had less pain than 74% of the chronic pain patients who received a placebo. This quantification, however, is only as good as the studies on which it is based, and it could be differentiated for each of the pain syndromes and antidepressants examined. Real analgesic qualities of antidepressive agents seemed to offer the most plausible and economical explanation for the effect, but the predominant importance of serotonin reuptake blocking was not confirmed. Finally, the meta-analysis appeared to be fruitful for the generation of new hypotheses, for making some recommendations for future research, and for proposing some provisional guidelines for the clinical use of antidepressants in chronic non-malignant pain.

Dynamic and static components of mechanical hyperalgesia in human hairy skin

Abstract: The principle finding of the present study is that there are two types of mechanical hyperalgesia developing in human hairy skin following injurious stimuli. Mechanical hyperalgesia comprises a dynamic component (brush-evoked pain, allodynia) signalled by large myelinated afferents and a static component (hyperalgesia to pressure stimuli) signalled by unmyelinated afferents. While the static component is only found in the injured area, the dynamic component also extends into a halo of undamaged tissue surrounding the injury. The irritant chemicals, mustard oil or capsaicin, were applied transdermally in 20 subjects to a patch (2 x 2 cm) of hairy skin. Both substances evoked burning pain and hyperalgesia to mechanical stimuli. While stroking normal skin with a cotton bud was perceived only as touch prior to chemical stimulation, there was a distinctly unpleasant sensation afterwards. This component of mechanical hyperalgesia persisted for at least 30 min and was present in the skin exposed to the irritants (primary hyperalgesia) as well as in a zone of untreated skin surrounding the injury (secondary hyperalgesia) measuring 38 +/- 4 cm2 after capsaicin. Pressure pain thresholds dropped to 55 +/- 8% of baseline level after mustard oil and to 46 +/- 9% after capsaicin. However, this drop of thresholds was short-lived, lasting 5 min following mustard oil but persisting more than 30 min following capsaicin treatment. The reduction of pressure pain thresholds was only observed for treated skin areas, but not in the surrounding undamaged tissue from where brush-evoked pain could be evoked. When pressure pain thresholds were lowered, the pain had a burning quality which differed distinctly from the quality of brush-evoked pain. On-going burning pain and both types of mechanical hyperalgesia were critically temperature dependent. Mildly cooling the skin provided instant relief from on-going pain, abolished brush-evoked pain and normalized pressure pain thresholds. Rewarming resulted in a reappearance of on-going pain and hyperalgesia. The effect of a nerve compression block of the superficial radial nerve on these sensations was tested in 14 experiments. When the ability to perceive light touch had been abolished, there was also no touch-evoked pain, indicating that this component of mechanical hyperalgesia is mediated by large-diameter primary afferents. At a later stage of the block when the subjects' ability to perceive cold stimuli had also been lost, application of cool stimuli still eliminated on-going burning pain, suggesting that pain relief afforded by cooling the skin acts at the peripheral receptor level and not by central masking.(ABSTRACT TRUNCATED AT 400 WORDS)

Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction

Abstract: Systemic application of lidocaine in rats suppressed ectopic impulse discharge generated both at sites of experimental nerve injury and in axotomized dorsal root ganglion (DRG) cells. ED50 for DRGs was significantly lower than for the injury site. Lidocaine doses effective at blocking ectopic discharge failed to block the initiation or propagation of impulses by electrical stimulation, and only minimally affected normal sensory receptors. This selectivity may account for the effectiveness of systemic local anesthetics and other drugs that share the same mechanism of action (notably certain anticonvulsants and antiarrhythmics), in the management of neuropathic paresthesias and pain. In addition, it may account for the prolonged analgesia sometimes obtained using regional local anesthetic block.

The effects of a non-competitive NMDA receptor antagonist, MK-801, on behavioral hyperalgesia and dorsal horn neuronal activity in rats with unilateral inflammation.

Abstract: The involvement of NMDA receptors in rats with peripheral inflammation and hyperalgesia was evaluated by administration of the non-competitive NMDA receptor antagonist, MK-801. Inflammation and hyperalgesia was induced by intradermal injection of complete Freund's adjuvant (CFA) or carrageenan into the left hind paw. The latency of paw withdrawal from a thermal stimulus was used as a measure of hyperalgesia in awake rats. MK-801 (1.6 mg/kg, i.p., or 31.5 micrograms, intrathecal) significantly attenuated thermal hyperalgesia and reduced its duration in comparison to saline-injected rats (P less than 0.05). The receptive field size of nociceptive-specific and wide-dynamic-range neurons in the superficial and deep spinal dorsal horn recorded 24 h after injection of CFA was significantly reduced to 73 +/- 6% (P less than 0.05, n = 8) and 74 +/- 4% (P less than 0.05, n = 8) of control values, respectively, by a cumulative dose of 3 mg/kg of MK-801 (i.v.). MK-801 (2 mg/kg) prevented the expansion of the receptive fields of dorsal horn neurons recorded 5 +/- 0.4 h (n = 5) after intradermal injection of CFA as compared to saline-injected rats (P less than 0.05). MK-801 had no significant effect on receptive field size of dorsal horn neurons in rats without CFA-induced inflammation but blocked a transient expansion of the receptive fields induced by 1 Hz, C-fiber intensity electrical stimulation of the sciatic nerve. The background activity and noxious heat-evoked response of dorsal horn neurons in rats with CFA-induced inflammation were primarily inhibited and noxious pinch-evoked activity was both facilitated and inhibited by the administration of MK-801. These results support the hypothesis that NMDA receptors are involved in the dorsal horn neuronal plasticity and behavioral hyperalgesia that follows peripheral tissue inflammation.

A limited arthritic model for chronic pain studies in the rat

Abstract: Freund's adjuvant induced polyarthritis in rats has been used extensively to study pain processes of long duration. There are limitations of this model for chronic studies of pain/arthritis since the severe systemicchanges provoke ethical concerns and also affect behaviour, physiology and biochemistry. Attempts to limit adjuvant-induced arthritis by plantar injection of the inoculum have been made. In this model, however, the process evolved to produce widespread polyarthritis if followed for the 6-plus-weeks necessary for chronic studies. Therefore, although it offers the researcher a reliable limited model of inflammation and nociception at the outset, for longer studies it may have all the disadvantages of the polyarthritic rat. The purpose of the present study was to produce a limited arthritic process in rats, stable over 6 weeks and suitable for behavioural and neurochemical studies of various chronic pain treatment methods. Injection (0.05 ml) of complete adjuvant containing 300 μg Mycobacterium butyricum in the tibio-tarsal joint produces a predictable monoarthritis, stable clinically and behaviourly from weeks 2 through 6 post injection. As revealed by clinical observations and X-ray examinations, the arthritis produced was limited anatomically, pronounced, prolonged and stable. A marked increase in sensitivity to paw pressure was seen in the affected limb. Animals gained weight and remained active, indicating little systemic disturbance as opposed to polyarthritic rats. We propose this limited model of arthritis as a suitable alternative to the polyarthritic rat for prolonged studies.

Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve. Excitatory amino acid antagonists

Abstract: This study evaluated the effects of spinally administered excitatory amino acid antagonists on the thermal hyperesthetic state induced by unilateral partial ligation of the sciatic nerve in the rat. The measured response was the latency to paw withdrawal of each hind paw after application of a focused heat lamp on the plantar surface of the paw through a glass plate upon which the animal stood. In this work, antagonists (MK801, dl -2-amino-5-phosphonovalerate, ketamine) of the N- methyl- d -aspartate receptor (NMDA), the glycine potentiation site at the NMDA receptor (5-chloro-indole-2-carboxylic acid) and non-NMDA receptor (kynurenic acid: g- d -glutamylaminomethyl sulphonate) were injected through chronically implanted lumbar intrathecal catheters in normal rats (no lesions) and in rats with unilateral constriction injury. In the normal rat study, NMDA and non-NMDA antagonists had little effect upon paw withdrawal latency at intrathecal doses which did not produce readily detectable motor weakness. In the hyperesthetic rat study, NMDA antagonists would temporarily eliminate the hyperesthetic state at doses below those which altered the response latency of the normal paw or which altered motor function. These results suggested that spinal NMDA receptors play an important role in the hyperesthetic state induced by peripheral nerve injury.

The NMDA-receptor antagonist CPP abolishes neurogenic ‘wind-up pain’ after intrathecal administration in humans

Abstract: Involvement of the NMDA receptor system in the transmission of nociceptive information, including the development of central sensitization and a wind-up phenomenon, has increased interest in NMDA-receptor antagonists as antinociceptive drugs. This case report describes the use of an NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) in a carefully selected patient with severe and intractable neurogenic pain in her left leg. The pain syndrome had components of a continuous deep pain, an allodynia, and a wind-up-like component, including afterdischarge and spread of painful sensations outside the territory of the injured nerve. After intrathecal (i.t.) administration of 200 nmol of CPP the continuous deep pain component and allodynia were unchanged, but the following 'wind-up' phenomenon with afterdischarge and spread of the pain sensation in the left half of the body was completely abolished. Another 500 nmol of CPP administered over 2 h did not improve pain relief. Pain thresholds for heat and cold stimulation, measured with a Marstock thermostimulator, did not change. There was no effect on blood pressure, heart rate, sensitivity, reflexes, coordination or motor performance. Psychotomimetic ketamine-like side effects developed 4 h after the last injection of CPP and were probably due to rostral spread of CPP. These early experiences with i.t. administration of NMDA-receptor antagonists to humans indicate that the NMDA-receptor system plays an important role in neurogenic pain and that antagonizing this system may be a useful way to obtain better pain control although psychotomimetic side effects due to rostral spread may be a problem.

Comparison of cognitive-behavioral group treatment and an alternative non-psychological treatment for chronic low back pain.

Abstract: This study was designed to investigate the relative efficacy of cognitive-behavioral group treatment, including relaxation training, in comparison with a control condition in a sample of 20 outpatients with chronic low back pain. Subjects in both conditions also received the same physiotherapy back-education and exercise program. The control condition included a control for the attention of the therapist in the cognitive-behavioral treatment. The combined psychological treatment and physiotherapy condition displayed significantly greater improvement than the attention-control and physiotherapy condition at post-treatment on measures of other-rated functional impairment, use of active coping strategies, self-efficacy beliefs, and medication use. These differences were maintained at 6 month follow-up on use of active coping strategies and, to a lesser degree, on self-efficacy beliefs and other-rated functional impairment.

The treatment of depression in chronic low back pain: review and recommendations

Abstract: The prevalence of major depression in patients with chronic low back pain (CLBP) is approximately three to four times greater than that reported in the general population. In spite of these high prevalence rates, there have been few systematic attempts to investigate the efficacy of treatment for major depression in patients with CLBP. While several studies have examined the efficacy of antidepressant medication and psychological treatment in patients with chronic pain, most of these studies have focused on treating chronic pain rather than depression. The few studies that have specifically addressed the treatment of depression in CLBP indicate that tricyclic antidepressants and cognitive-behavioral approaches may be effective means of treating depressed chronic pain patients. Clinical issues related to diagnostic confounds, rehabilitation outcome, and conceptualizations of the relation between pain and depression are discussed. It is argued that, in patients with clinical levels of depression, treatment modalities specifically targeting depressive symptomatology deserve serious consideration as an integral component of pain management programs.

Statistical analysis of drug combinations for synergism

Abstract: Testing a pair of drugs for synergism requires determination of the potency of the combination and comparison of this potency with that of a theoretically additive combination. The potency of a drug or of a mixture is measured as a dose (or concentration) that produces a specified level of effect such as one-half the maximum effect (E,,,). Most often this dose, denoted either D,, (for graded data) or ED50 (for quanta1 data), is obtained from an appropriate analysis of dose-effect data that yields a smooth curve. Because doses have frequently been found to be log-normally distributed, the smooth curve analyzed is often plotted with log(dose) or log(concentration) on the abscissa for both graded and quanta1 curves. When data are quantal, the proportion or percent of subjects responding is often converted to probits. Probit analysis, a weighted regression procedure, is deeply rooted in the pharmacologic literature. It permits the use of 0 and 100% responses in the regression analysis and thus uses all the data. Discussions of probit analysis are contained in Hewlett and Plackett (1979) and Tallarida and Murray (19871, the latter provided a computational algorithm and computer program for getting the mean ED50 and confidence limits. The most complete discussion of probit analysis is in the standard work by Finney 0971). In contrast to the weighted regression procedure of probit analysis, analysis of graded data is usually conducted in the mid-range of effects where the error variance is approximately constant. Thus, simple linear regression of effect on log dose is employed and yields the mean log(D,,) and variance, V[log(D,,)], from which the mean D,, and VCD,,) may be calculated. It is convenient to have a simple notation for potency, whether ED50 or D,,, or doses based on other levels of effect (e.g., D,, and ED70 when the level of effect is 70% of E,,,). We here denote this dose by z”, with appropriate subscripts to identify each individual drug or the mixture. Of course, in all comparisons and analyses that utilize these quantities, it is understood that the same common level of effect applies. Most often this will be one-half of E,,, so that z * will be a D,, or ED50 value, but other levels of effect are sometimes used (Ossipov et al. 1990). It should also be mentioned that non-linear curve fitting algorithms that compute z *, its variance and confidence limits from dose-response data may be employed instead of simple linear regression or probit analysis. However, the latter is especially suitable to the analysis of quanta1 data because it allows the use of 0 and 100% responses in a method of estimation based on maximum likelihood (Finney 1971). In the following it will be assumed that potency estimates (z *) and related statistical quantities have been obtained by a valid analysis of the data.

Cephalic muscle tenderness and pressure pain threshold in a general population

Abstract: Tenderness and pain thresholds in pericranial muscles were studied in a general population. A random sample of 1000 adults aged 25-64 years was drawn as part of the Glostrup Population Studies, and 740 adults were examined. This study was part of a multifacetted, epidemiological study of different headache disorders according to the new headache classification. Manual palpation and pressure pain threshold with an electronic pressure algometer were performed by observers blinded to other information such as the person's history of headache, previous illness and mental state. The muscles most commonly tender to manual palpation were the lateral pterygoid (55%), the trapezius (52%), and the sternocleido-mastoid muscles (51%). Females were more tender than men in all the muscles examined by manual palpation. In total, the young age group was more tender than the old age group (P = 0.03). Pressure pain thresholds on temporal muscles showed lower thresholds in women than in men (P less than 10(-3)), and in the total population thresholds increased with age (P less than 0.05). No side-to-side difference in tenderness by manual palpation was found, while the right side showed increased pain thresholds in right-handed individuals (P less than 10(-4)). No side-to-side difference was found in left-handed persons. This study provides data about the normal population and forms the necessary basis for evaluating the importance of muscle tenderness in headache subjects and other selected groups.

Hypnosis or cognitive behavioral training for the reduction of pain and nausea during cancer treatment: a controlled clinical trial.

Abstract: Few controlled clinical trials have tested the efficacy of psychological techniques for reducing cancer pain or post-chemotherapy nausea and emesis. In this study, 67 bone marrow transplant patients with hematological malignancies were randomly assigned to one of four groups prior to beginning transplantation conditioning: (1) hypnosis training (HYP); (2) cognitive behavioral coping skills training (CB); (3) therapist contact control (TC); or (4) treatment as usual (TAU; no treatment control). Patients completed measures of physical functioning (Sickness Impact Profile; SIP) and psychological functioning (Brief Symptom Inventory; BSI), which were used as covariates in the analyses. Biodemographic variables included gender, age and a risk variable based on diagnosis and number of remissions or relapses. Patients in the HYP, CB and TC groups met with a clinical psychologist for two pre-transplant training sessions and ten in-hospital "booster" sessions during the course of transplantation. Forty-five patients completed the study and provided all covariate data, and 80% of the time series outcome data. Analyses of the principal study variables indicated that hypnosis was effective in reducing reported oral pain for patients undergoing marrow transplantation. Risk, SIP, and BSI pre-transplant were found to be effective predictors of inpatient physical symptoms. Nausea, emesis and opioid use did not differ significantly between the treatment groups. The cognitive behavioral intervention, as applied in this study, was not effective in reducing the symptoms measured.

Stimulation of craniofacial muscle afferents induces prolonged facilitatory effects in trigeminal nociceptive brain-stem neurones

Abstract: Stimulation of small-diameter afferents supplying deep tissues has been shown to increase the excitability of spinal cord neurones responding to cutaneous afferent inputs This facilitation has been implicated as integral central mechanisms of deep pain that may contribute to the tenderness and spread and/or referral of pain following injury of deep tissues In view of the recent documentation of deep craniofacial afferent inputs, as well as cutaneous afferent inputs to the trigeminal (V) spinal tract nucleus, we wished to determine the effects of deep inputs excited by the small-fibre irritant mustard oil on trigeminal nociceptive neurones The extracellular activity of single brain-stem neurones was recorded in subnuclei caudalis and oralis of the V spinal tract nucleus of anaesthetized rats The neurones were classified as low-threshold mechanosensitive (LTM), wide dynamic range (WDR) and nociceptive specific (NS) on the basis of their cutaneous mechanoreceptive field properties and their responses evoked by electrical stimulation of their cutaneous afferent inputs Injection of 5% mustard oil (2-5 microliters) into the deep masseter muscle produced a facilitatory effect in 12 of 27 nociceptive neurones tested in caudalis and in 5 of 12 nociceptive neurones in oralis This effect was reflected in an expansion of the cutaneous mechanoreceptive field, an increase in spontaneous activity or an increase in responsivity to electrical stimulation of cutaneous afferent inputs to the neurones The facilitation was reversible and typically became apparent within 3-5 min of the injection, reached its peak at 5-10 min, and lasted for 20-30 min(ABSTRACT TRUNCATED AT 250 WORDS)

Individual variability in the response to different opioids: report of five cases☆

Abstract: Although it is widely appreciated that patients can demonstrate highly variable responses to different opioid drugs, there have been few detailed descriptions of this phenomenon. To illustrate this variability, we present 5 patients, 4 with cancer pain and 1 with non-malignant pain, who underwent dose titration with more than 1 opioid and developed markedly different responses to each. In every case, dose escalation led to successful treatment with 1 opioid and to intolerable side effects without adequate relief with others. The existence of this individual variability in the response to different opioids has important implications for both clinical practice and current understanding of opioid pharmacology in man. It contradicts the view that any opioid is inherently more efficacious than any other, suggests that patients who fail to obtain adequate pain relief at maximally tolerated doses of 1 opioid may benefit from an alternative drug, and underscores the potential importance of genetic factors as a determinant of opioid response.

Assessment of acute pediatric pain : do child self-report, parent ratings, and nurse ratings measure the same phenomenon ?

Abstract: The purpose of this study was to determine the factors that are associated with child, parent, and nurse ratings of acute pediatric pain and distress during venipuncture. The behavior of eighty-five pediatric cancer patients during venipuncture was recorded by trained raters, and their observations were compared with ratings of pain and distress obtained from parents, pediatric patients, and pediatric nurses. Regression analyses indicated that ratings made by the child, parent, and nurse reflect different perspectives. Nurses' ratings were based upon overt distress, parents' ratings reflected their subjective perception of the child's pain, and the child's self-report was associated with the child's chronologic age.

Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial

Abstract: Amitriptyline (AT) relieves some patients with postherpetic neuralgia (PHN). Many patients suffer side effects and better therapies are necessary. The aim of this study was to evaluate the efficacy of maprotiline (MT) (noradrenergic) compared to AT (mixed noradrenergic and serotonergic) in this disorder. Thirty-five patients entered a randomized, double-blind, crossover trial of these two agents. We found that MT relieved PHN in many patients but was not as effective as AT. Side effects were troublesome with both agents. Relief of steady pain, brief pain and pain on tactile stimulation occurred. Four groups of responses were identified. Some patients reported relief with both agents, some with neither agent and others with only one of the drugs. Most patients were not depressed and analgesia was observed to occur without change in depression ratings in most patients who responded. This result provides evidence that in some patients AT may act via a selective noradrenergic mechanism in relieving PHN and that individuals may differ in the balance and type of neurotransmitters inhibiting pain. Selective noradrenergic agents may be effective if AT fails.

Sensory testing of pathophysiological mechanisms of pain in patients with reflex sympathetic dystrophy.

Abstract: The incidence of 3 sensory abnormalities was studied among 17 patients with a diagnosis of reflex sympathetic dystrophy (RSD) and 14 patients with persistent limb pain following trauma; the extent to which the 3 abnormalities were associated with each other and with the intensity of spontaneous clinical pain were also studied. These abnormalities included (1) heat-induced hyperalgesia (54.8% of 31 patients tested); (2) low-threshold A beta-mediated (45.2%) or high-threshold (54.8%) mechanical allodynia; and (3) slow temporal summation of mechanical allodynia (10 of 29 patients tested). These 3 sensory abnormalities occurred to widely varying extents and were not reliably associated with each other. As hypothesized, patients with temporal summation had significantly more intense spontaneous pain than those who did not demonstrate this sensory characteristic. In contrast, the presence or absence of thermal hyperalgesia and type of allodynia did not appear to influence the intensity of spontaneous pain. These results indicate that variable types of primary afferents (i.e., A beta versus A delta, C) and/or varying extents of abnormal spatial summation mechanisms trigger pain responses among RSD patients and that at least one of these, slow temporal summation, is likely to contribute to the intensity of a patient's ongoing pain.

Morphine-3-glucuronide may functionally antagonize morphine-6-glucuronide induced antinociception and ventilatory depression in the rat.

Abstract: The effects of the major morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, on nociception were assessed by the tail-flick, hot-plate and writhing tests in the rat. Morphine-3-glucuronide (M3G) 1.1 × 10 −9 mol (0.5 μg) or saline was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.) followed by a second injection of 2.0 × 10 −10 mol (0.1 μg) or 2.0 × 10 −11 mol (0.01 μg) morphine-6-glucuronide (M6G) 10 min later. Administration of M3G (i.c.v.) significantly attenuated the antinociceptive effects of M6G in the hot-plate test. After i.t. administration, the antinociceptive effect of M6G in all three tests was significantly reduced in the M3G pretreated group compared to the group receiving saline. The ventilatory effects of 4.0 × 10 −9 −10 × 10 −8 mol (2–5 μg) M6G and 1.7−2.2 × 10 −8 mol (8–10 μg) M3G given i.c.v. were studied by a whole-body plethysmographic technique in halothane anaesthetized rats. Separate groups of rats received M3G followed by M6G injection or vice versa. In animals receiving M3G there was a prevention or attenuation of the M6G induced depression of respiratory frequency, tidal volume and minute ventilation compared to control groups receiving M6G in combination with saline. These results show that M3G may functionally antagonize the central antinociceptive effects as well as the ventilatory depression induced by M6G. Interestingly, M3G was more potent in antagonizing the M6G-induced analgesia after i.t. administration than that after i.c.v. administration, which may suggest that the spinal cord is more sensitive to the non-opioid excitatory effects of M3G than supraspinal structures.

Chronic pain-related syndrome in rats after ischemic spinal cord lesion: a possible animal model for pain in patients with spinal cord injury.

Abstract: We examined a pain-related syndrome, which includes mechanical allodynia and autotomy, in rats after ischemic spinal cord injury photochemically induced by laser irradiation for 5–20 min This procedure results in an acute allodynia-like phenomenon which lasts for several days and is possibly related to dysfunction of the GABAB system in the spinal cord In some animals this is followed by a chronic allodynia-like symptom with an onset varying between 1 week and 15 months after injury, expressed as a clearly painful reaction to light pressure applied to a skin area at or near the dermatome of the injured spinal segments In the majority of rats the allodynia persists over several months, in some cases accompanied by autotomy of the hind paws Pharmacological studies indicated that the allodynia in the majority of rats could be relieved by systemic tocainide (75 mg/kg) Morphine was only effective at a sedative dose (5 mg/kg) The allodynia was not relieved by baclofen, muscimol, clonidine or carbamazepine Low-dose systemic pentobarbital (5 mg/kg) had a slight beneficial effect Guanethidine (20 mg/kg sc) did not abolish the allodynia in most of the rats Histological examination revealed massive damage in the spinal cord The dorsal roots of the irradiated segments were also injured No morphological abnormalities were seen in the dorsal root ganglia The mechanism that may account for this chronic pain-related syndrome in spinally injured rats probably involves abnormalities in the central nervous system The allodynia seen in chronic spinally injured rats was similar to some painful symptoms in patients after spinal cord injury or stroke It is suggested that the chronic allodynia-like phenomenon may represent an animal model for studying the mechanisms of chronic central pain

Facet joint injection and facet nerve block: a randomised comparison in 86 patients with chronic low back pain.

Abstract: Eighty-six patients with refractory chronic low back pain were randomly assigned to receive either facet joint injection or facet nerve block, using local anaesthetic and steroid. There was no significant difference in the immediate response. The duration of response after facet joint injection was marginally longer than after facet nerve block (P < 0.05 1 month after infiltration), but for both groups the response was usually short-lived; by 3 months only 2 patients continued to report complete pain relief. Patients who had complained of pain for more than 7 years were more likely to report good or excellent pain relief than those with a shorter history (P < 0.005), but no other clinical feature was of value in predicting the response to infiltration. Facet joint injections and facet nerve blocks may be of equal value as diagnostic tests, but neither is a satisfactory treatment for chronic back pain.

The relationship between pain sensitivity and blood pressure in normotensives.

Abstract: Hypertension has been found to be related to decreased sensitivity to painful stimuli The current study explored whether this relationship extends into the normotensive range of blood pressures Resting blood pressures were assessed in 60 male normotensives Subjects then underwent a 1 min finger pressure pain stimulation trial Pain ratings were inversely related to resting systolic blood pressure This relationship was unrelated to emotional state or coping styles Multiple regression analyses indicated that over one-third of the variance in pain ratings can be accounted for by resting blood pressure, coping style, and emotional state

Pain response to perineuromal injection of normal saline, epinephrine, and lidocaine in humans.

Abstract: Rat neurons have shown an increase of spontaneously active fibers to systemically administered potassium channel blocking agents such as tetraethylammonium chloride (TEA) and gallamine. Neuroma formation and spontaneous activity have been associated with autotomy in rats and pain in humans. To evaluate the chemosensitivity of human neurons to potassium channel blocking agents, 9 subjects with neuroma pain underwent perineuromal injection in a single-blinded fashion of normal saline, gallamine, and lidocaine. Sodium had no effect on control pain levels, while gallamine significantly increased and lidocaine significantly decreased pain from control levels. Three of 4 patients with accompanying phantom limb pain noted an increase in pain after the injection of gallamine. The data suggest that peripheral input plays a modulating but not solitary role in both neuroma and phantom limb pain. Agents which increase potassium channel permeability or decrease sodium influx would be predicted to decreased perceived pain.

Calcitonin in phantom limb pain: a double-blind study.

Abstract: Salmon calcitonin (s-CT) has been shown to be a valuable analgesic in phantom limb pain (PLP) in several case reports. To evaluate these findings a double-blind crossover comparison of s-CT treatment versus placebo was initiated. Twenty-one out of 161 patients who had undergone major amputations and developed severe PLP 0-7 days after surgery were included in the study. For each patient a matched pair of infusions was prepared containing either 200 IU of s-CT or placebo. Group I (n = 11) was first given s-CT and group II (n = 10) placebo. When PLP reached a level of more than 3 on a numeric analogue scale (NAS) the first infusion was administered. The second infusion (crossover) or more infusions were given when the pain level again exceeded more than 3 on NAS. Using s-CT infusion, PLP was eased from a median of 7 to 4 on NAS in both groups (P less than 0.001), regardless of whether s-CT or placebo was given first. Placebo, however, did not change pain scores (median 7 on NAS, P greater than 0.1). In the s-CT group, but not in the placebo group, 4 individuals remained pain free without a second infusion. Any further treatment was performed with s-CT. One week after the first PLP treatment 19 patients (90%) had pain relief of more than 50%, 16 (76%) were completely pain free, and 15 (71%) never experienced PLP again. One year later 8 out of the 13 surviving patients (62%) still had more than 75% PLP relief. After 2 years PLP exceeded 3 on NAS in 5 individuals (42%), and the remaining 12 patients presented the same PLP as after 1 year. In conclusion, s-CT is a valuable treatment for PLP in the early postoperative period.