Rheumatoid arthritis (RA) is an inflammatory autoimmune condition typified by systemic inflammation targeted toward synovial joints. Inhibition of proinflammatory networks by disease-modifying antirheumatic drugs, eg, methotrexate and biologic therapies, including tumor necrosis factor-α inhibitors, often leads to suppression of disease activity observed at the clinical level. However, despite the era of widespread use of disease-modifying treatments, there remain significant groups of patients who continue to experience pain. Our study formulated a pain assessment tool in the arthritis clinic to assess feasibility of measurements including the visual analog scale (VAS) and painDETECT to assess multimodal features of pain in people with established RA (n=100). Clinical measures of disease activity (Disease Activity Score in 28 Joints [DAS28]) were also recorded. Our data showed that despite the majority of subjects on at least one disease-modifying agent, the majority of patients reported severe pain (54%) by VAS, despite well-controlled clinical disease, with mean DAS28 2.07±0.9. Using the painDETECT questionnaire, 67% of patients had unlikely neuropathic pain. A significant proportion of subjects (28%) had possible neuropathic pain and 5% had features of likely neuropathic pain by painDETECT scoring. We found a positive correlation between VAS and painDETECT (R2=0.757). Of note, the group who had likely or probable neuropathic pain also showed significantly increased pain reporting by VAS (P<0.01). Subjects who were clinically obese (body mass index >30) also had statistically higher proportions of pain reporting (VAS 89.0±0.7 mm) compared with subjects who had a normal body mass index (VAS 45.2±21.8 mm), P<0.05. Our findings suggest that multimodal features of pain perception exist in RA, including neuropathic and sensitization elements, perhaps explaining why a subgroup of people with RA continue to experience ongoing pain, despite their apparent suppression of inflammation.

Hypothalamic 5HT concentrations are transiently lower in male compared to female Wistar rats in the second week post partum (pp) and our previous findings have shown that pharmacologically potentiating 5HT activity over this period feminizes certain aspects of sexually differentiated behaviours in adult males and androgenized females. In order to investigate whether neonatal testosterone and 5HT interact to influence physiological and morphological brain sexual differences, females, androgenized females and males were treated with the 5HT2 agonist (-) [2,5 dimethoxy-4-iodophenyl]-2-amino propane HCl [(-) DOI], over days 8-16 pp. In androgenized females (250 microg testosterone proprionate, day 2 pp) (-) DOI prevented the delay in vaginal opening, but did not prevent the androgen-induced constant oestrus in females treated with 100 microg TP, day 2 pp. (-) DOI overcame the neonatal androgen effect in suppressing the positive feedback of ovarian steroids in a few males and androgenized females. (-) DOI had a feminizing effect on the volume of the anteroventral periventricular nucleus (normally smaller in males), by significantly increasing its volume in male and androgenized females. It also had a significant antagonistic effect on the testosterone-induced increase in the volume of the sexually dimorphic nucleus of the preoptic area in males and androgenized females. These findings support the view that raised 5HT activity in the second week of life antagonizes the masculinizing effect of neonatal testosterone.

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