Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

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Central sensitization: implications for the diagnosis and treatment of pain.

e thank Tuttolomondo et al. (1)fortheirinterestinourstudy(2).In response, we would like toclarify several points. First, coding ofstrokes has been ongoing in the Nurses’Health Study since 1976. We have nothad funding to implement coding byTOAST (Trial of Org 10172 in AcuteStroke Treatment) classiﬁcation (3) buthope to do so in the future. In an internalcomparisonofcodingbyPerthcriteria(4)versus TOAST, the concordance rate forlacunar infarction was very high (91%);however, a percentage of large artery in-farctions as classiﬁed by Perth coding cri-teria was classiﬁed as “unknown type” byTOAST criteria due to inconclusive ca-rotid Doppler ﬁndings. Thus, it is possi-ble that differences in stroke classiﬁcationmay have lead to slightly higher risk esti-mates for large artery infarction in ourpopulation.Second, our results are consistentwithdiabetesbeingastrongriskfactorforlacunar infarction. As shown in Table 2 ofthe article, incidence rates for lacunar in-farction were higher than for large arteryinfarction among women with type 2 di-abetes (50 and 36 per 100,000 person-years, respectively), and risk estimateswere also slightly higher for lacunar thanlarge artery infarction (3.6 vs. 2.7 in age-adjusted analyses) compared with womenwithout diabetes.Third, both fatal and nonfatal infarc-tions were included, but only ﬁrst eventswere considered. Thus, our methods dodifferfromsomehospital-basedstudiesinthat only ﬁrst stroke events were in-cluded. As stated in the article, resultswere similar for conﬁrmed (medicalrecords)andprobable(letterortelephonecorroboration) cases, thus the combinedresults were presented (see p. 1731, col-umn 2).Finally, as suggested by Tuttolomondoet al., it is possible that there are sex differ-ences in the strength of association be-tweendiabetesandlargearteryinfarction.Our results are limited to women, and weencourage further sex-speciﬁc evalua-tions of these associations.

Prospective Study of

Research studies focusing on the fear-avoidance model have expanded considerably since the review by Vlaeyen and Linton (Vlaeyen J. W. S. & Linton, S. J. (2000). Fear-avoidance and its consequences in chronic musculoskeletal pain: a state of the art. Pain, 85(3), 317--332). The fear-avoidance model is a cognitive-behavioral account that explains why a minority of acute low back pain sufferers develop a chronic pain problem. This paper reviews the current state of scientific evidence for the individual components of the model: pain severity, pain catastrophizing, attention to pain, escape/avoidance behavior, disability, disuse, and vulnerabilities. Furthermore, support for the contribution of pain-related fear in the inception of low back pain, the development of chronic low back pain from an acute episode, and the maintenance of enduring pain, will be highlighted. Finally, available evidence on recent clinical applications is provided, and unresolved issues that need further exploration are discussed.

The fear-avoidance model of musculoskeletal pain: current state of scientific evidence.

The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.

/pdf/biphasic-dose-response-in-low-level-light-therapy-2gubtp7dyk.pdf

Biphasic Dose Response in Low Level Light Therapy

The Mechanisms of Manual Therapy in the Treatment of Musculoskeletal Pain: A Comprehensive Model

Hypersensitivity to a variety of sensory stimuli is a feature of persistent whiplash associated disorders (WAD). However, little is known about sensory disturbances from the time of injury until transition to either recovery or symptom persistence. Quantitative sensory testing (pressure and thermal pain thresholds, the brachial plexus provocation test), the sympathetic vasoconstrictor reflex and psychological distress (GHQ-28) were prospectively measured in 76 whiplash subjects within 1 month of injury and then 2, 3 and 6 months post-injury. Subjects were classified at 6 months post-injury using scores on the Neck Disability Index: recovered ( 30). Sensory and sympathetic nervous system tests were also measured in 20 control subjects. All whiplash groups demonstrated local mechanical hyperalgesia in the cervical spine at 1 month post-injury. This hyperalgesia persisted in those with moderate/severe symptoms at 6 months but resolved by 2 months in those who had recovered or reported persistent mild symptoms. Only those with persistent moderate/severe symptoms at 6 months demonstrated generalised hypersensitivity to all sensory tests. These changes occurred within 1 month of injury and remained unchanged throughout the study period. Whilst no significant group differences were evident for the sympathetic vasoconstrictor response, the moderate/severe group showed a tendency for diminished sympathetic reactivity. GHQ-28 scores of the moderate/severe group were higher than those of the other two groups. The differences in GHQ-28 did not impact on any of the sensory measures. These findings suggest that those with persistent moderate/severe symptoms at 6 months display, soon after injury, generalised hypersensitivity suggestive of changes in central pain processing mechanisms. This phenomenon did not occur in those who recover or those with persistent mild symptoms.

Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery

Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery.

Cervical mobilisation: concurrent effects on pain, sympathetic nervous system activity and motor activity

Dizziness and/or unsteadiness are common symptoms of chronic whiplash-associated disorders. This study aimed to report the characteristics of these symptoms and determine whether there was any relationship to cervical joint position error. Joint position error, the accuracy to return to the natural head posture following extension and rotation, was measured in 102 subjects with persistent whiplash-associated disorder and 44 control subjects. Whiplash subjects completed a neck pain index and answered questions about the characteristics of dizziness. The results indicated that subjects with whiplash-associated disorders had significantly greater joint position errors than control subjects. Within the whiplash group, those with dizziness had greater joint position errors than those without dizziness following rotation (rotation (R) 4.5 degrees (0.3) vs 2.9 degrees (0.4); rotation (L) 3.9 degrees (0.3) vs 2.8 degrees (0.4) respectively) and a higher neck pain index (55.3% (1.4) vs 43.1% (1.8)). Characteristics of the dizziness were consistent for those reported for a cervical cause but no characteristics could predict the magnitude of joint position error. Cervical mechanoreceptor dysfunction is a likely cause of dizziness in whiplash-associated disorder.

https://espace.library.uq.edu.au/view/UQ:66459/UQ66459_OA.pdf

Dizziness and unsteadiness following whiplash injury: characteristic features and relationship with cervical joint position error.

Predictors of outcome following whiplash injury are limited to socio-demographic and symptomatic factors, which are not readily amenable to secondary and tertiary intervention. This prospective study investigated the predictive capacity of early measures of physical and psychological impairment on pain and disability 6 months following whiplash injury. Motor function (ROM; kinaesthetic sense; activity of the superficial neck flexors (EMG) during cranio-cervical flexion), quantitative sensory testing (pressure, thermal pain thresholds, brachial plexus provocation test), sympathetic vasoconstrictor responses and psychological distress (GHQ-28, TSK, IES) were measured in 76 acute whiplash participants. The outcome measure was Neck Disability Index scores at 6 months. Stepwise regression analysis was used to predict the final NDI score. Logistic regression analyses predicted membership to one of the three groups based on final NDI scores ( 30 moderate/severe pain and disability). Higher initial NDI score (1.007-1.12), older age (1.03-1.23), cold hyperalgesia (1.05-1.58), and acute post-traumatic stress (1.03-1.2) predicted membership to the moderate/severe group. Additional variables associated with higher NDI scores at 6 months on stepwise regression analysis were: ROM loss and diminished sympathetic reactivity. Higher initial NDI score (1.03-1.28), greater psychological distress (GHQ-28) (1.04-1.28) and decreased ROM (1.03-1.25) predicted subjects with persistent milder symptoms from those who fully recovered. These results demonstrate that both physical and psychological factors play a role in recovery or non-recovery from whiplash injury. This may assist in the development of more relevant treatment methods for acute whiplash.

Michele Sterling

Papers

Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery

Sensory hypersensitivity occurs soon after whiplash injury and is associated with poor recovery.

Cervical mobilisation: concurrent effects on pain, sympathetic nervous system activity and motor activity

Dizziness and unsteadiness following whiplash injury: characteristic features and relationship with cervical joint position error.

Physical and psychological factors predict outcome following whiplash injury.