Showing papers in "Pain in 1990"

A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury

Abstract: Partial nerve injury is the main cause of causalgiform pain disorders in humans. We present here a novel animal model of this condition. In rats we unilaterally ligated about half of the sciatic nerve high in the thigh. Within a few hours after the operation, and for several months thereafter, the rats developed guarding behavior of the ipsilateral hind paw and licked it often, suggesting the possibility of spontaneous pain. The plantar surface of the foot was evenly hyperesthetic to non-noxious and noxious stimuli. None of the rats autotomized. There was a sharp decrease in the withdrawal thresholds bilaterally in response to repetitive Von Frey hair stimulation at the plantar side. After a series of such stimuli in the operated side, light touch elicited aversive responses, suggesting allodynia to touch. The withdrawal thresholds to CO2 laser heat pulses were markedly lowered bilaterally. Suprathreshold noxious heat pulses elicited exaggerated responses unilaterally, suggesting thermal hyperalgesia. Pin-prick evoked such exaggerated responses bilaterally (mechanical hyperalgesia). In a companion report, we show that these abnormalities critically depend on the sympathetic outflow. Based on the immediate onset and long-lasting perpetuation of similar symptoms, such as touch-evoked allodynia and hyperalgesia, and the resemblance of the contralateral phenomena to 'mirror image' pains in some humans with causalgia, we suggest that this preparation may serve as a model for syndromes of the causalgiform variety that are triggered by partial nerve injury and maintained by sympathetic activity.

The faces pain scale for the self-assessment of the severity of pain experienced by children: Development, initial validation, and preliminary investigation for ratio scale properties

Abstract: Altogether 553 children (195 first graders, mean age 6.8 years, and 358 third graders, mean age 8.7 years) participated in the development of a self-report measure to assess the intensity of children's pain. The first step was the derivation, from children's drawings of facial expressions of pain, of 5 sets of 7 schematic faces depicting changes in severity of expressed pain from no pain to the most pain possible. With the set of faces that achieved the highest agreement in pain ordering, additional studies were conducted to determine whether the set had the properties of a scale. In one study, children rank-ordered the faces on 2 occasions, separated by 1 week. All 7 faces were correctly ranked by 64% (retest 1 week later, 61%) of grade 1 children and by 86% (retest 89%) of grade 3 children. In a second study, the faces were presented in all possible paired combinations. All 7 faces were correctly placed by 62% (retest 86%) of the younger and by 75% (retest 71%) of the older subjects. A third study asked children to place faces along a scale: a procedure allowing a check on the equality of intervals. The fourth study checked on whether pain was acting as an underlying construct for ordering the faces in memory. We asked whether children perceived the set as a scale by asking if memory for an ordered set of faces was more accurate than for a random set. The final study checked, with 6-year-old children, the test-retest reliability of ratings for recalled experiences of pain. Overall, the faces pain scale incorporates conventions used by children, has achieved strong agreement in the rank ordering of pain, has indications that the intervals are close to equal, and is treated by children as a scale. The test-retest data suggest that it may prove to be a reliable index over time of self-reported pain.

The Pain Disability Index: psychometric properties

Abstract: This paper reports two studies of chronic pain patients (n = 444) relevant to the psychometric properties of the Pain Disability Index (PDI), a self-report instrument that has been used to assess the degree to which chronic pain interferes with various daily activities. In the first study, patients with high PDI scores reported more psychological distress (P less than 0.001), more severe pain characteristics (P less than 0.001), and more restriction of activities (P less than 0.001) than patients with low PDI scores, findings supportive of the construct validity of the measure. Further, a multiple regression showed that a linear combination of 9 variables predicted PDI scores (R = 0.74): time spent in bed, psychosomatic symptoms, stopping activities because of pain, work status, pain duration, usual pain intensity, quality of life, pain extent, and education. This study also showed differences for age and gender on disability. The second study involved 46 patients who had undergone inpatient treatment for their pain conditions. The study revealed modest test-retest reliability for the instrument. It also showed the PDI to be associated with the levels of pain behavior exhibited by these patients. The findings of both studies generally support the reliability and validity of the PDI as a brief measure of pain-related disability. Questions regarding its test-retest reliability and lack of association with certain pain behaviors are discussed, as are suggestions for future research.

Breakthrough pain: definition, prevalence and characteristics

Abstract: In the cancer population, the term breakthrough pain typically refers to a transitory flare of pain in the setting of chronic pain managed with opioid drugs. The prevalence and characteristics of this phenomenon have not been defined, and its impact on patient care is unknown. We developed operational definitions for breakthrough pain and its major characteristics, and applied these in a prospective survey of patients with cancer pain. Data were collected during a 3 month period from consecutive patients who reported moderate pain or less for more than 12 h daily and stable opioid dosing for a minimum of 2 consecutive days. Of 63 patients surveyed, 41 (64%) reported breakthrough pain, transient flares of severe or excruciating pain. Fifty-one different pains were described (median 4 pains/day; range 1-3600). Pain characteristics were extremely varied. Twenty-two (43%) pains were paroxysmal in onset; the remainder were more gradual. The duration varied from seconds to hours (median/range: 30 min/1-240 min), and 21 (41%) were both paroxysmal and brief (lancinating pain). Fifteen (29%) of the pains were related to the fixed opioid dose, occurring solely at the end of the dosing interval. Twenty-eight (55%) of the pains were precipitated; of these, 22 were caused by an action of the patient (incident pain), and 6 were associated with a non-volitional precipitant, such as flatulence. The pathophysiology of the pain was believed to be somatic in 17 (33%), visceral in 10 (20%), neuropathic in 14 (27%), and mixed in 10 (20%). Pain was related to the tumor in 42 (82%), the effects of therapy in 7 (14%), and neither in 2 (4%). Diverse interventions were employed to manage these pains, with variable efficacy. These data clarify the spectrum of breakthrough pains and indicate their importance in cancer pain management.

Visceral pain: a review of experimental studies.

Abstract: This paper reviews clinical and basic science research reports and is directed toward an understanding of visceral pain, with emphasis on studies related to spinal processing. Four main types of visceral stimuli have been employed in experimental studies of visceral nociception: (1) electrical, (2) mechanical, (3) ischemic, and (4) chemical. Studies of visceral pain are discussed in relation to the use and 'adequacy' of these stimuli and the responses produced (e.g., behavioral, pseudoaffective, neuronal, etc.). We propose a definition of an adequate noxious visceral stimulus and speculate on spinal mechanisms of visceral pain.

The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions.

Abstract: In recent years, the observation that the response of patients to opioid drugs may be influenced by properties inherent in the pain or pain syndrome, such as its pathophysiology, has evolved into the belief that certain types of pain e.g., neuropathic pains, may be unresponsive to these drugs. This concept has important implications for both clinical practice and basic understanding of opioid mechanisms. We critically evaluate opioid responsiveness, particularly as it relates to neuropathic pain, and propose a clinically relevant definition and a paradigm for its investigation. The paradigm is illustrated by analgesic responses to opioid infusion in 28 patients with neuropathic pains and by a detailed presentation of the pharmacokinetic and pharmacodynamic relationships in one of these patients, whose central pain responded promptly to an infusion of hydromorphone. From this analysis, we hypothesize that (1) opioid responsiveness in man can be defined by the degree of analgesia achieved during dose escalation to either intolerable side effects or the occurrence of ‘complete’ or ‘adequate’ analgesia; (2) opioid responsiveness is a continuum, rather than a quantal phenomenon; (3) opioid responsiveness is determined by a diverse group of patient characteristics and pain-related factors, as well as drug-selective effects; and (4) a neuropathic mechanism may reduce opioid responsiveness, but does not result in an inherent resistance to these drugs. Given the complexity of factors contributing to opioid responsiveness and the observation that outcome cannot be reliably predicted, opioids should not be withheld on the assumption that pain mechanism, or any other factor, precludes a favorable response. Both the clinical use of opioids and paradigms to investigate opioid responsiveness should include dose escalation to maximally tolerated levels and repeated monitoring of analgesia and other effects.

Further evidence for ‘pain-related’ behaviours in a model of unilateral peripheral mononeuropathy

Abstract: A model of experimental peripheral neuropathy producing pain-related disorders has recently been described in the rat. The present study aimed to investigate, using a different and quantifiable behavioural approach, the abnormal pain-related sensations in the animals. The neuropathy was produced by 4 ligatures tied loosely around the common sciatic nerve. 6-8 days after surgery, most of the rats exhibited pain-related disorders ipsilateral to the sciatic ligation, which became maximal 2 weeks after surgery. Mechanical noxious stimulation (pinching of the hind paw) revealed hyperalgesia in all the animals. Rats also exhibited allodynia when tested with the vocalization threshold test to paw pressure (mean vocalization thresholds were 65.5 +/- 3.6% of the preoperative control, P less than 0.01, n = 95). Tests using heat (40, 42, 44, 46 degrees C) and cold (10 degrees C) stimulation (immersion of the rat's hind paw in a bath until it was observed to struggle) indicated hyperalgesia to noxious heat (decrease of 30% in the immersion duration (ID) at a temperature of 46 degrees C), and allodynia to non-noxious heat (decrease of 30% in the temperature of the struggle threshold) and to cold stimulation (decrease by 40% in the ID). In addition, the animals showed modifications in the spontaneous postures of the affected hind paw in a natural setting, suggesting a 'spontaneous' pain-related behaviour (the mean 'pain' rating, derived from the technique used for the formalin test and numbered 0-5, was 2.8 +/- 0.4, P less than 0.01, n = 12). Lastly, sensitized responses were observed to mechanical stimulation after thermal stimulation in the non-noxious range applied to the lesioned but not the non-lesioned paw. The time course of pain-related disorders was comparable whatever the behavioural test, with recovery 2 months after surgery. These results clearly show that the neuropathy produces abnormal pain-related disorders in the rat, which are reminiscent of those observed in some human neuropathies.

Graded chronic pain status: an epidemiologic evaluation.

Abstract: In epidemiologic research on chronic pain, differentiation of recurrent, persistent and disabling pain states is critical in the investigation of burden, natural history, effective intervention and causal processes. We report population-based data concerning the development and evaluation of a graded classification of pain status. In a probability sample of 1016 health maintenance organization enrollees, recurrent or persistent pain was observed in 45%; severe and persistent pain in 8%; severe and persistent pain with 7 or more days of pain-related activity limitation in 2.7%; and severe, persistent pain with activity limitation and 3 or more indicators of pain dysfunction in 1.0% of the population sample. Graded chronic pain status was associated with psychological impairment, unfavorable appraisal of health status, and frequency of use of pain medications and health care. The presence of severe and persistent pain increased the likelihood of multiple indicators of pain dysfunction, but there was considerable heterogeneity in pain dysfunction among persons with comparable pain experience. Our data suggest grading chronic pain in terms of 3 axes: time (persistence); severity; and impact (disability and dysfunctional illness behaviors).

The formalin test in mice: effect of formalin concentration.

Abstract: The effect of different formalin concentrations on the nociceptive response in the formalin test was examined in mice. Subcutaneous formalin injection induces 2 distinct periods of high licking activity: an early phase lasting the first 5 min, and a late phase lasting 20-30 min after the injection. Formalin concentrations of 0.02-0.2% induced only the early phase, while concentrations of 1% or more induced both the early phase and the late phase. The ability of the test to show the antinociceptive effect of morphine and acetylsalicylic acid was similar for high and low formalin concentrations. For both these analgesics, a lower dose was needed to induce antinociception in the late phase than in the early phase using the same formalin concentration. Indomethacin had no effect in the early phase. In the late phase indomethacin induced antinociception when 1% formalin was used, while no significant effect was observed using 5% formalin. Clear histological changes in the paw were demonstrated after formalin concentrations that induced both phases. Lower formalin concentrations induced only very small changes. Using a low formalin concentration (0.2%), repeated testing using the same paw could be performed at intervals of 1 week without any significant change in the response. It was concluded that the formalin concentration should be kept as low as possible to minimize the suffering of the animal. Formalin concentrations of 0.05-0.2% are recommended for studying the early phase. Formalin concentrations of 1% or higher have to be used when studying the nociceptive response in the late phase.

Pain 'memories' in phantom limbs: review and clinical observations.

Abstract: This paper reviews reports of phantom limb sensations which resemble somatosensory events experienced in the limb before amputation. It also presents descriptions of this phenomenon in 68 amputees who took part in a series of clinical studies. These somatosensory memories are predominantly replicas of distressing pre-amputation lesions and pains which were experienced at or near the time of amputation, and are described as having the same qualities of sensation as the pre-amputation pain. The patients who experience these pains emphasize that they are suffering real pain which they can describe in vivid detail, and insist that the experience is not merely a cognitive recollection of an earlier pain. Reports of somatosensory memories are less common when there has been a discontinuity, or a pain-free interval, between the experience of pain and amputation. Among the somatosensory memories reported are cutaneous lesions, deep tissue injuries, bone and joint pain and painful pre-amputation postures. The experience of somatosensory memories does not appear to be related to the duration of pre-amputation pain, time since amputation, age, gender, prosthetic use, level of amputation, number of limbs amputated, or whether the amputation followed an accident or illness. The results suggest that somatosensory inputs of sufficient intensity and duration can produce lasting changes in central neural structures which combine with cognitive-evaluative memories of the pre-amputation pain to give rise to the unified experience of a past pain referred to the phantom limb. Implications for pre- and post-operative pain control are discussed.

The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms

Abstract: SummaryThe effect of the selective serotonin reuptake inhibitor paroxetine on diabetic neuropathy symptoms was examined in comparison to imipramine and placebo in a randomised, double-blind, cross-over study. Paroxetine was given as a fixed dose of 40 mg/day, while the dose of imipramine was adjuste

Transsynaptic degeneration in the superficial dorsal horn after sciatic nerve injury: effects of a chronic constriction injury, transection, and strychnine

Abstract: The lumbar and cervical spinal dorsal horns of adult rats with a chronic (8 days) constriction injury of the sciatic nerve on one side (and a sham operation on the other) were examined for signs of transsynaptic degeneration. The incidence of neurons with signs of degeneration (pyknosis and hyperchromatosis; 'dark neurons') was significantly increased in the lumbar dorsal horn on both sides. The ipsilateral lumbar increase was significantly greater than the contralateral increase. There was no increase in the incidence of dark neurons in the cervical dorsal horns of the same rats. The distribution of lumbar dark neurons was similar bilaterally. The majority of the dark neurons were found in the sciatic nerve's territory in laminae I-II. A second group of rats received the same surgery but in addition received a series of 7 daily subconvulsive doses of strychnine. Dark neurons were again found bilaterally (with ipsilateral predominance) in the sciatic nerve's territory in lumbar laminae I-II, but the incidence was significantly greater than that found in the group that did not receive strychnine. The same result was obtained in a third group of strychnine-treated rats when the sham operation was omitted. Thus the appearance of contralateral dark neurons is not dependent on unintentional nerve damage created by the sham procedure. An additional group of rats was sacrificed 8 days after receiving a unilateral sciatic nerve transection, a contralateral sham operation, and the 7 daily strychnine injections. There was no increase in the incidence of dark neurons in any of these rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The rat paw formalin test: comparison of noxious agents.

Abstract: A comparison was made of the spontaneous nociceptive behaviors elicited by s.c. injection into the rat hind paw of the following 8 irritants: acetic acid, carrageenan, formalin, kaolin, platelet-activating factor, mustard oil (given topically), serotonin, and yeast. Two distinct quantifiable behaviors indicative of pain were identified: flinching/shaking of the paw and hindquarters and licking/biting of the injected paw. These behaviors were prolonged and intense after formalin and acetic acid. Formalin-induced flinching was biphasic across time, a finding potentially useful for the study of both acute and tonic pain. Of the remaining test agents, only yeast caused significant spontaneous behavioral activity, which was of low intensity but long duration. Different time-courses for nociceptive behavior and development of edema were demonstrated for formalin, acetic acid and yeast. It is therefore unlikely that these endpoints are causally related. Overall, the present data strongly support the use of formalin as a noxious stimulus in tonic pain research.

The Role of Conditioning and Verbal Expectancy in the Placebo Response

Abstract: Both conditioning and expectancy models have been offered in recent years as explanations for the placebo response. Following our earlier work on conditioning placebo responses in human subjects the current study examined the relative contribution made by conditioning and verbal expectancy. Group 1 received a Combined Expectancy and Conditioning Manipulation; group 2 received Expectancy Alone; group 3, Conditioning Alone; and group 4 was the control group. Subjects' responses were compared with and without a placebo cream, using iontophoretic pain stimulation. The results suggest that conditioning was more powerful than verbal expectancy in creating a placebo response.

Chronic musculoskeletal pain and depressive symptoms in the general population. An analysis of the 1st National Health and Nutrition Examination Survey data.

Abstract: Chronic pain and depression frequently occur together. A selection bias afflicts all hospital clinic and family practice populations in which this relationship has been examined. We report here some of the results from civilian populations outside institutions, examined in the United States in national surveys. The findings are based upon the recollection of individuals with respect to the period of 12 months prior to interview and upon the occurrence of depression in the previous week as indicated by the answers to the Depression Scale of the Centre for Epidemiologic Studies (CES-D). They indicate that 14.4% of the United States population between the ages of 25–74 suffer from definite chronic pain related to the joints and musculoskeletal system. Another 7.4% have some pain of uncertain duration. Eighty-three percent of the definite pain group received treatment. Chronic pain subjects scored significantly higher than normals on the CES-D (10.68 ± S.E.M. 0.76 vs. 8.05 ± 0.23, P < 0.01) with subjects with pain of uncertain duration scoring similar to the definite chronic pain population (11.13 ± 0.76). Using a high cut-off score for depression, 18% of the population with chronic pain were found to have depression. This is in contrast to 8% of the population who did not have chronic pain.

Neonatal facial and cry responses to invasive and non-invasive procedures

Abstract: Evaluation of pain in neonates is difficult due to their limited means of communication. The aim was to determine whether behavioural reactions of cry and facial activity provoked by an invasive procedure could be discriminated from responses to non-invasive tactile events. Thirty-six healthy full-term infants (mean age 2.2 h) received 3 procedures in counterbalanced order: intramuscular injection, application of triple dye to the umbilical stub, and rubbing thigh with alcohol. Significant effects of procedure were found for total face activity and latency to face movement. A cluster of facial actions comprised of brow bulging, eyes squeezed shut, deepening of the naso-labial furrow and open mouth was associated most frequently with the invasive procedure. Comparisons between the 2 non-invasive procedures showed more facial activity to thigh swabbing and least to application of triple dye to the umbilical cord. Acoustic analysis of cry showed statistically significant differences across procedures only for latency to cry and cry duration for the group as a whole. However, babies who cried to two procedures showed higher pitch and greater intensity to the injection. There were no significant differences in melody, dysphonation, or jitter. Methodological difficulties for investigators in this area were examined, including criteria for the selection of cries for analysis, and the logical and statistical challenges of contrasting cries induced by different conditions when some babies do not always cry. It was concluded that facial expression, in combination with short latency to onset of cry and long duration of first cry cycle typifies reaction to acute invasive procedures.

Comparisons between patients' and nurses' assessment of pain and medication efficacy in severe burn injuries.

Abstract: In order to provide burn patients with adequate pain relief, the nurses must be able to accurately evaluate the patients' pain levels and to assess whether sufficient analgesia is achieved or not. The present study examined this issue by comparing the pain ratings in 42 patients hospitalized for burn injuries and 42 nurses. The patient and the attending nurse were asked to rate, independently of each other, the intensity of the pain felt by the patient during a therapeutic procedure and at rest. When analgesic medication was given prior to the procedure, both the patients and the nurses were asked to estimate the degree of pain relief. All ratings were obtained using visual analogue and verbal scales. The results revealed significant but small correlations between the nurses' and patients' ratings. Frequently, the nurses underestimated or overestimated the patients' pain. Discrepancies were also observed in the evaluation of pain medication efficacy, the nurses showing a tendency to overestimate the degree of pain relief. The accuracy of the nurses' perception did not vary as a function of the patients' age, socioeconomic status or burn severity. However, the number of years of experience in burn-nursing had a significant influence on the nurses' estimation of the patients' pain during therapeutic procedures. Theoretical and clinical implications of these results are discussed with a particular emphasis on the need to implement systematic procedures to assess pain and success of analgesia. Additional recommendations to optimize pain management in burn patients are also made.

Memory for pain: a review

Abstract: This paper reports a qualitative review of the literature on memory for pain. Most research has focused on the accuracy of memory for pain intensity. There is some evidence that recall is moderately accurate but this conclusion is tentative because of significant methodological problems. There is also some evidence that recall of acute pain is more accurate than recall of chronic pain and we make some suggestions as to why this difference might occur. We conclude that further research on memory for pain should be informed by reference to methodological practices developed in cognitive psychology and embedded within an appropriate theoretical framework.

The robustness of an empirically derived taxonomy of chronic pain patients.

Abstract: There is currently no classification system for chronic pain patients that has achieved consensus. The lack of a classification that is used consistently across settings has impaired advance of knowledge and treatment of chronic pain patients. Recently, an empirically derived multivariate classification system, the Multiaxial Assessment of Pain (MAP) patients, has been developed. In this paper, the generalizability of the MAP system was evaluated by contrasting the MAP classification of 3 common but diverse chronic pain syndromes, namely, low back pain, headache, and temporomandibular disorders. The results indicate that although the proportion of patients classified into the 3 subgroups of the MAP taxonomy differ, the profiles based on the pattern of interrelationship among the assessment scales were remarkably similar. These data suggest that the psychosocial and behavioral responses associated with chronic pain are common to diverse samples of pain patients despite differences in demographic characteristics and medical diagnosis. The implications of these results for research and clinical practice are discussed. The potential utility of a polydiagnostic approach using more traditional medically based classifications such as proposed by the IASP (Merskey, H., Pain, Suppl. 3 (1986) S1-S225) complemented by classification based on the MAP psychosocial-behaviorally based taxonomy are examined.

Prolonged relief of neuralgia after regional anesthetic blocks. A call for further experimental and systematic clinical studies.

Abstract: Thirty-eight consecutive patients with neuralgia after peripheral nerve injury were treated with one or two series of peripheral local anesthetic blocks. All patients experienced an initial total relief of ongoing pain for 4–12 h. Evoked pain (hyperalgesia or allodynia), which occurred in 17 patients, was blocked simultaneously with the spontaneous pain. In 18 patients the analgesia outlasted the conduction block and there was a period of complete pain relief of 12–48 h in 13 patients and of 2–6 days in the other 5. In 8 patients there was a second phase of analgesia of 4 h to 6 days duration occurring within 12 h of pain recurrence. Thus, mono- or biphasic prolonged complete analgesia occurred in 25 out of 38 patients. A prolonged analgesia may be the result of a central action of the local anesthetic at the spinal level after intra-axonal incorporation and centripetal axoplasmic transport. To test this hypothesis, an experimental study with [3H]lidocaine was performed in 6 rats. The radioactive local anesthetic was injected into one hind limb foot with the other side serving as a control. Tissue samples from the peripheral nerve, nerve root and the lumbosacral spinal cord segment were analyzed for radioactivity using a scintillation counter technique at various time intervals after the [3H]lidocaine injection. There was a low grade of activity in all samples and no difference between the test side and the control side. Thus these experiments provided no evidence in support of this hypothesis. Various alternative peripheral and central mechanisms are discussed. Further studies specifically directed to these alternatives and with longitudinal controls are prompted.

Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord.

Abstract: Excitatory amino acid (EAA) receptor agonists were tested for their effect on identified rat spinal neurons. Only 75% of the spinal neurons tested increased their firing rate in response to iontophoretic application of one or more of the EAA receptor agonists, N-methyl-d-aspartate (NMDA), quisqualate (Quis), (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid HBr (AMPA), and kainate (KA). NMDA and Quis or AMPA activated primarily nociceptive neurons (60% of these neurons were projection neurons) in the rat spinal cord. KA-activated neurons were primarily classified as low threshold neurons. Both NMDA and AMPA, at subthreshold doses, significantly increased neuronal responses to peripheral noxious mechanical stimulation; NMDA also significantly increased neuronal responses to peripheral noxious thermal stimulation. Iontophoretically applied phencyclidine (PCP) decreased NMDA-induced firing in 100% of the cells tested while Quis-induced firing was blocked by PCP in only 33% of the cells tested. The reported analgesic effects of PCP in humans may result from a spinal action involving its well documented interaction with NMDA receptors.

Capsaicin : actions on nociceptive C-fibres and therapeutic potential

Abstract: Recent work on the excitatory action of capsaicin on somatic and visceral afferent neurones shows that depolarization is selective for C-fibre polymodal nociceptor afferents and involves opening a non-selective cation channel. Exposure to significantly suprathreshold amounts of capsaicin causes permanent degeneration of C-fibre afferents in adult rats. Functional changes in rats (hypalgesia, diminished neurogenic inflammation) are likely to be a direct consequence of the loss of C-fibre nociceptors, and so are the reductions in neuropeptide levels that follow adult capsaicin treatment. Clinical trials of topical capsaicin treatment for post-herpetic neuralgia have yielded promising results. The selective nature of the action of capsaicin in reducing just C-nociceptor activity may make it particularly useful for treating pain states triggered by C-fibre input.

An emotional component analysis of chronic pain.

Abstract: The present study sought to determine the relative contribution of frustration, fear, anger and anxiety, to the unpleasantness and depression pain patients experience. Sixty-nine women and 74 men, with an average age of 47 years, were included. Patients underwent psychological evaluation which included use of the Minnesota Multiphasic Personality Inventory (MMPI), Beck Depression Inventory (BDI), and 7 visual analog scales (VAS) measuring degree of emotional unpleasantness, pain intensity, anxiety, frustration, fear, anger and depression. Test-retest reliability coefficients were significant for the negative feeling VAS yielding an average reliability coefficient of 0.82. Analyses relating the negative feeling state VAS to pain unpleasantness and depression indices from the MMPI (scale 2) and BDI (sum score) yielded significant canonical correlations. Multiple regression was used to clarify the relationships between negative feeling VAS, pain-related unpleasantness, and indices of depression. After statistically controlling for intensity of pain, anxiety and frustration predicted unpleasantness. Regression analyses indicate that anger is an important concomitant of the depression that pain patients experience. The results suggest that anger and frustration are critical concomitants of the pain experience. Treatment techniques specifically targeting anger and frustration in these patients may prove efficacious.

A psychophysiological study in humans using phasic colonic distension as a noxious visceral stimulus.

Abstract: Psychophysiological experiments were performed in 9 humans using constant-pressure, phasic, graded distension (30 sec, 20–70 mm Hg) of the sigmoid colon as a visceral stimulus. Reliable cardiovascular (pressor), respiratory and visceromotor responses in addition to reports of pressure/pain sensations were evoked by colonic distension in 8 of the 9 subjects. The pressure/pain sensations were referred to the lower abdomen, lower back and perineum and their intensity quantified using a visual analogue scale. Responses to colonie distension were graded and increased with repeated distensions at the same intensity (60 mm Hg). The area of referral as indicated by subject drawings increased with repeated distensions as did the intensity of the subjects' sensory and affective descriptors of the sensation. Five of the subjects differentiated between ‘pressure’ and ‘pain’ sensations evoked by colonic distension; the intensity of the ‘pain’ sensation accelerated during the distending stimulus whereas the ‘pressure’ sensation was typically stable or adapting during the distending stimulus.

Pharmacological versus non-pharmacological prophylaxis of recurrent migraine headache: a meta-analytic review of clinical trials.

Abstract: In order to generate information about the relative effectiveness of the most widely used pharmacological and non-pharmacological interventions for the prophylaxis of recurrent migraine (i.e., propranolol HCl and combined relaxation/thermal biofeedback training), meta-analysis was used to integrate results from 25 clinical trials evaluating the effectiveness of propranolol and 35 clinical trials evaluating the effectiveness of relaxation/biofeedback training (2445 patients, collectively). Meta-analysis revealed substantial, but very similar improvements have been obtained with propranolol and with relaxation/biofeedback training. When daily recordings have been used to assess treatment outcome, both propranolol and relaxation/biofeedback have yielded a 43% reduction in migraine headache activity in the average patient. When improvements have been assessed using other outcome measures (e.g., physician/therapist ratings), improvements observed with each treatment have been about 20% greater. In both cases, improvements observed with propranolol and relaxation/biofeedback have been significantly larger than improvement observed with placebo medication (14% reduction) or in untreated patients (no reduction). Meta-analysis thus revealed substantial empirical support for the effectiveness of both propranolol and relaxation/biofeedback training, but revealed no support for the contention that the two treatments differ in effectiveness. These results suggest that greater attention should be paid to determining the relative costs and benefits of widely used pharmacological and non-pharmacological treatments.

A prospective survey of reactions to blood tests by children and adolescents.

Abstract: A sample of 171 children and adolescents aged 3-17 years requiring venepuncture for blood sampling were asked to report on their pain and anxiety and were observed immediately before and during blood drawing. Depending on the measures used, 36-64% of children from 3 to 6 years old experienced moderate to severe distress from blood drawing. Multiple regression analysis revealed that age and the parents' prediction of how upset the child would feel before the blood test was a significant predictor of the observed distress and the self-report of pain. Experience with previous needle procedures did not add significantly to the prediction of distress. Identification of children at high risk to respond poorly to painful medical procedures is discussed.

Postoperative pain therapy: a survey of patients' expectations and their experiences.

Abstract: For 2 months elective surgical patients (n = 259) were asked preoperatively about their expectations of pain and pain relief. At both 24 and 72 h after their surgery they were asked about their pain and pain control. The analgesics they received were monitored for the first 72 h. The survey revealed that patients do not have the necessary knowledge about pain relief to contribute effectively in their own pain management. Analgesics administered intermittently were generally effective when given, however, the dosing interval was too long for the agents used resulting in frequent reports of poor pain relief. We conclude that patients need better education on postoperative pain control therapy. Medical staff could prescribe, and nursing staff administer, analgesics more effectively.

Neglected factors in chronic pain treatment outcome studies--referral patterns, failure to enter treatment, and attrition.

Abstract: An increasing number of chronic pain treatment outcome studies have appeared in the literature. In general, these studies support the efficacy of multidisciplinary pain programs, as well as specific treatment modalities such as biofeedback and relaxation. Reviews of this literature have tended to be cautiously optimistic. Some concerns, however, have been raised about the methodological adequacy of these studies, particularly in terms of the lack of control groups, the brief duration of follow-up periods, and the vague criteria used for establishing the success of the therapeutic interventions. Other factors that mitigate conclusions regarding the generalizability of the favorable results reported need to be considered. In this paper 3 rarely discussed topics that are implicit within most treatment outcome studies and that need to be given greater attention are examined. These topics include: 1. (1) referral patterns to pain clinics (who are referred to pain clinics, when, and how representative is the referred sample?); 2. (2) failure to enter treatment (e.g., exclusion criteria, lack of available financial support to cover the cost of treatment, patient's refusal to accept recommendations), and consequently, the representativeness of the treated sample; 3. (3) patient's attrition. In this paper we discuss each of these factors as they underscore important qualifications that have to be made in evaluating treatment outcome studies.

Studies of heat pain sensation in man: perception thresholds, rate of stimulus rise and reaction time

Abstract: Afferent impulse frequency, one of the determinants of subjective magnitude of sensation, varies with the rate of rise of stimulus intensity: the faster the increase in stimulus energy, the higher the frequency of firing for a given amount of energy. This predicts that the steeper the stimulus ramp the lower will be the threshold for perception. While such inverse relation holds for myelinated fibre mediated cold sensation and mechanical pressure sensation, the opposite has been reported for unmyelinated fibre mediated heat pain and cold pain sensations. These paradoxical results intuitively suggest possible reaction time artefact. Indeed, a fixed time interval that includes conduction of the impulses to the brain, central processing and efferent conduction, intervenes between sufficient peripheral stimulus and the voluntary signal in reaction to subjective experience. As stimulus temperature continues to rise along this time, an artefactually high threshold reading results: the steeper the temperature rise, the larger will be the artefact, particularly for submodalities with longer reaction time. The present study compared heat pain threshold, obtained through a method that involves reaction time participation, with heat pain thresholds obtained bypassing reaction time. It was found in 16 volunteers that: (a) Heat pain thresholds decreased as the rate of temperature rise increased when reaction time was not a factor (P less than 0.001). (b) Heat pain thresholds determined through the method involving reaction time participation were significantly higher than those obtained bypassing reaction time (P less than 0.01). Such difference increased with increasing rates of temperature rise. (c) Peripheral conduction velocity calculated from average reaction time was found to be approximately 0.6 m/sec.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy.

Abstract: In a double-blind controlled design, 7 patients with painful diabetic neuropathy received lidocaine 5 mg/kg or saline intravenously over a period of 30 min. Thermal sensibility quantified by thermotest was not affected by lidocaine. In 3 of the patients nociceptive flexion reflex thresholds could be determined. The threshold was increased by lidocaine and returned to pre-infusion level within 10 days. Lidocaine also increased the threshold in 4 healthy subjects, but did not affect the Hoffmann reflex. These results suggest that lidocaine exerts its pain-relieving effect on the spinal level in diabetic neuropathy.