title: Characterisation of capsaicin-induced mechanical hyperalgesia as a marker for altered nociceptive processing in patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is characterised by pain and tenderness not only over inflamed or damaged joints, but also over apparently normal tissues. Experimental models suggest that these features results from changes of sensitivity within both peripheral and central neurones, but direct evidence from human disease is lacking. At present, most clinical studies have evaluated overall pain experience rather than activity within components of the nociceptive pathway. Therefore, the aim of this study was to assess the use of a capsaicin-based technique to quantify changes of neuronal sensitivity in patients with RA. First 20 microliters of capsaicin in solution (0.03 mg/ml) was applied topically for 30 min to apparently normal skin on the forearm of control subjects and patients with RA. The subsequent development of mechanical hyperalgesia to pinprick stimuli was then measured at various time points using a 74.4-mN von Frey hair. The relationship between the area of hyperalgesia and a number of clinical measures was determined. Capsaicin-induced mechanical hyperalgesia was found to decline with age in normal subjects (r = 0.47, P < 0.01). The development of hypearlgesia had a similar time course in normal subjects and patients with RA. The maximum area of hyperalgesia, however, was substantially larger in 35 RA patients; 254.3 +/- 20.7 cm2, compared with 35 normal controls; 109 +/- 7.5 cm2 (P < 0.001). An association was apparent between hyperalgesic area and a composite score of joint tenderness (r = 0.47, P < 0.01), but not with overall pain score or a systemic marker of inflammation. These results provide evidence for enhanced sensitisation of a population of sensory fibres in RA. Peripheral sensory activity over the forearms of rheumatoid patients has previously been shown to be normal and the results suggest the presence of enhanced central mechanisms in this disorder. The correlation between capsaicin-induced hyperalgesia and joint tenderness in the RA patients implies that joint symptoms arise partially as a result of central, and not exclusively peripheral, factors. The study supports the use of capsaicin-based techniques to explore nociceptive mechanisms in clinical disorders characterised by chronic pain.
authors.affiliation: Bone and Joint Research Unit, St Bartholomew's and Royal London School of Medicine, UK.
authors.forename: V H
authors.initials: VH
authors.lastname: Morris
authors.forename: S C
authors.initials: SC
authors.lastname: Cruwys
authors.forename: B L
authors.initials: BL
authors.lastname: Kidd
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000503:physiopathology*; D002211:Capsaicin; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced* / Q000188:drug therapy*; D007052:Ibuprofen / Q000627:therapeutic use; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects*; D017288:Pain Threshold / Q000187:drug effects; D012881:Skin Temperature / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002211:Capsaicin; D007052:Ibuprofen