Parallel clinical and behavioural studies of adjuvant-induced arthritis in the rat: Possible relationship with ‘chronic pain’

Abstract

The course of adjuvant-induced arthritis was followed, over an 11-week postinoculation period, in Sprague-Dawley rats, using both clinical and behavioural methods of study. Clinical observations included body weight, diameters of radiocarpal and tibiotarsal joints and radiological analysis of forepaws, hindpaws and vertebrae. Behavioural observations included those of spontaneous behaviour - mobility, exploring, rearing, penis licking and scratching - and of pain-related tests - the foot-bend procedure and Randall-Selitto test. In general, the time course of the disease could be divided into 4 stages, viz. a preclinical, an acute, a postacute and a recovery stage. The preclinical stage (first week) was characterized by discrete radiological lesions of the forepaws and a slight increase in the threshold for struggle triggered by foot pressure, but, above all, by no change in the other parameters. The acute stage (weeks 2–4) was clearly defined by a pause in body weight gain and by dramatic behavioural changes: a lack of mobility and exploring behaviour, a profound increase in scratching behaviour and signs of hyperalgesia. During this period, hindpaw and forepaw joint diameters increased dramatically. The behavioural modifications peaked at the same time (week 4) as there was an acceleration in the radiological abnormalities (soft tissue swelling, demineralization and erosion of bone extremities and joint space narrowing) which had begun during week 3. During the postacute stage (weeks 5–8), body weight and behavioural reactions began to return towards control values, but joint diameters and radiological scores either continued to increase or remained constant. During the recovery stage (weeks 9–11), behavioural scores and body weight returned to control values while the mean joint diameters remained constant and there was a slight decrease in the radiological scores. In spite of the complexity of the model used in these studies, it appeared quite clear that the acute phase of the disease was characterized by the onset of clinical symptoms and dramatic changes in behaviour, all of which could be related to the occurrence of pain; signs of pain were still present, albeit weaker, in the postacute phase. Such observations, taken together, help to validate adjuvant arthritis as an experimental model of chronic pain in Sprague-Dawley rats.