Contralateral hyperalgesia and allodynia following intradermal capsaicin injection in man.

OBJECTIVES: Contralateral responses to unilateral stimuli have been well described in animal models. These range from central sensitization to peripheral inflammatory responses. Our aim was to test for contralateral responses following unilateral intradermal capsaicin injection in man. METHODS: Three groups were investigated. A healthy volunteer group (1) was injected with capsaicin into the volar aspect of one forearm. A group of patients with RA (2) was also injected with capsaicin. A control group of healthy volunteers (3) was not injected with capsaicin. All groups were tested for hyperalgesia and allodynia every 10 min for 1 h following the injection using quantitative sensory testing. RESULTS: A total of 9/14 healthy volunteers (Group 1) and 10/14 patients with RA (Group 2) demonstrated contralateral sensitization that subsided within 1 h following intradermal capsaicin injection. A total of 2/23 control subjects (Group 3) demonstrated positive responses with the monofilaments. The frequency of the contralateral responses in the experimental groups compared with the control group is significant (P < 0.05). The peak hyperalgesia was relatively delayed contralaterally compared with the ipsilateral side (35 min vs 15 min). The area of sensitization, where present, was reduced compared with the ipsilateral side (5-50%). CONCLUSIONS: This is the first demonstration of a contralateral response following a unilateral stimulus in man. Bilateral neural pathways mediating contralateral responses may have a role in the pathophysiology of chronically painful or inflammatory diseases and a confounding influence on using the contralateral limb as a control experimentally. We did not find that a systemic inflammatory disease sensitized for this phenomenon.

Phantoms in rheumatology.

This paper examines rheumatology pain and how it may relate to amputee phantom limb pain (PLP), specifically as experienced in rheumatoid arthritis, fibromyalgia and complex regional pain syndrome (CRPS). Clinical findings, which suggest cortical sensory reorganization, are discussed and illustrated for each condition. It is proposed that this sensory reorganization generates pain and altered body image in rheumatology patients in the same manner as has previously been hypothesized for amputees with PLP; that is via a motor/sensory conflict. The correction of this conflict through the provision of appropriate visual sensory input, using a mirror, is tested in a population of patients with CRPS. Its analgesic efficacy is assessed in those with acute, intermediate and chronic disease. Finally, the hypothesis is taken to its natural conclusion whereby motor/sensory conflict is artificially generated in healthy volunteers and chronic pain patients to establish whether sensory disturbances can be created where no pain symptoms exists and exacerbated when it is already present. The findings of our studies support the hypothesis that a mismatch between motor output and sensory input creates sensory disturbances, including pain, in rheumatology patients and healthy volunteers. We propose the term 'ominory' to describe the central monitoring mechanism and the resultant sensory disturbances as a dissensory state.

Simulating sensory-motor incongruence in healthy volunteers: implications for a cortical model of pain.

OBJECTIVES: Conflict between motor-sensory central nervous processing has been suggested as one cause of pain in those conditions where a demonstrable or local nociceptive aetiology cannot be convincingly established (e.g. complex regional pain syndrome type 1, repetitive strain injury, phantom limb pain and focal hand dystonia). The purpose of this study was to discover whether pain could be induced in pain-free healthy volunteers when this conflict was generated transiently in a laboratory setting. METHODS: Forty-one consecutively recruited healthy adult volunteers without a history of motor or proprioceptive disorders performed a series of bilateral upper and lower limb movements whilst viewing a mirror/whiteboard, which created varied degrees of sensory-motor conflict during congruent/incongruent limb movements. A qualitative method recorded any changes in sensory experience. RESULTS: Twenty-seven subjects (66%) reported at least one anomalous sensory symptom at some stage in the protocol despite no peripheral nociceptive input. The most frequent symptoms occurred when incongruent movement was performed whilst viewing the reflected limb in the mirror condition, the time of maximum sensory-motor conflict. Symptoms of pain were described as numbness, pins and needles, moderate aching and/or a definite pain. Other sensations included perceived changes in temperature, limb weight, altered body image and disorientation. There were indications that some individuals were more susceptible to symptom generation than others. CONCLUSIONS: Our findings support the hypothesis that motor-sensory conflict can induce pain and sensory disturbances in some normal individuals. We propose that prolonged sensory-motor conflict may induce long-term symptoms in some vulnerable subjects.

Referred sensations in patients with complex regional pain syndrome type 1.

OBJECTIVES: This study sought to explore and characterize referred sensations (RS) in patients with complex regional pain syndrome (CRPS) type 1 and test the hypothesis that pain in CRPS is associated with central sensory changes. METHODS: Subjects underwent standardized neurological examination involving light touch, pinprick and vibration sense with eyes closed and then with eyes open. The subjects described the location and sensation emanating from the stimulated site and whether they experienced any sensations (similar or different) elsewhere. RESULTS: Five of 16 subjects recruited demonstrated RS. These were experienced in real time, were modality specific (touch and pinprick) and were located on the body part immediately adjacent, on Penfield's cortical homunculus, to the stimulated site. The RS were diminished or absent when the subject visualized the stimulated area. They disappeared when stimulation ceased and on clinical improvement. CONCLUSIONS: This is the first report of RS in CRPS and provides further evidence of central reorganization in what was previously thought to be a peripheral disorder.

Joint stiffness in a phantom limb: evidence of central nervous system involvement in rheumatoid arthritis.

OBJECTIVE: The nature and cause of perceived joint stiffness (PJS), a well-established and defining symptom of rheumatoid arthritis (RA), remains unclear. We hypothesized that changes in the central nervous system (CNS) may determine and maintain this subjective experience of stiffness in a limb even after it is amputated. To test this hypothesis, patients with a phantom limb (PL) who had experienced characteristic RA stiffness prior to amputation were systematically investigated. METHODS: Three patients with a current diagnosis of RA and lower limb amputation were investigated to determine the nature and pattern of pain and stiffness in their PL and intact limb. In addition to standard physical examination, pain and stiffness severity was measured using visual analogue scales for both limbs. The duration and timing of stiffness were also recorded for each limb. RESULTS: In all three cases, the pattern of perceived RA stiffness was similar for the intact limb and the PL. All three patients described stiffness in their PL which mirrored that of physical RA joint symptoms in terms of quality, frequency, diurnal variation, location, distribution and response to medication [non-steroidal anti-inflammatory drug (NSAID), corticosteroid, opiate and disease-modifying anti-rheumatic drug (DMARD)]. Unilateral exercise (or attempted exercise) relieved stiffness only in the limb being exercised. CONCLUSION: The extent to which the subjective experience of perceived stiffness could be dissociated from the assumed original peripheral source was strikingly illustrated in RA patients with phantom limbs. We suggest that the PJS characteristic of RA is generated and maintained by secondary plastic changes in the CNS, although causally related to the initial peripheral rheumatoid disease process.

A controlled pilot study of the utility of mirror visual feedback in the treatment of complex regional pain syndrome (type 1).

BACKGROUND: We assessed mirror visual feedback (MVF) to test the hypothesis that incongruence between motor output and sensory input produces complex regional pain syndrome (CRPS) (type 1) pain. METHODS: Eight subjects (disease duration > or =3 weeks to < or =3 yr) were studied over 6 weeks with assessments including two controls (no device and viewing a non-reflective surface) and the intervention (MVF). Pain severity and vasomotor changes were recorded. RESULTS: The control stages had no analgesic effect. MVF in early CRPS (< or =8 weeks) had an immediate analgesic effect and in intermediate disease (< or =1 yr) led to a reduction in stiffness. At 6 weeks, normalization of function and thermal differences had occurred (early and intermediate disease). No change was found in chronic CRPS. CONCLUSIONS: In early CRPS (type 1), visual input from a moving, unaffected limb re-establishes the pain-free relationship between sensory feedback and motor execution. Trophic changes and a less plastic neural pathway preclude this in chronic disease.