A time course analysis of the changes in spontaneous and evoked behaviour in a rat model of neuropathic pain

Abstract

We have previously demonstrated that scratching was significantly increased in a rat model of polyarthritis and that this could be reversed by morphine and electrical stimulation of pain-modulating brain areas. We therefore proposed that scratching might represent a parameter of chronic pain. In this study, we examined the spontaneous behaviour of rats in a model of peripheral neuropathy induced by loosely tying 4 ligatures around the right common sciatic nerve. In half of the animals (N = 7), the ligatures were made with resorbable sutures and, in the other half (N = 7), with non-resorbable sutures of the same size. Postoperatively, scratching was significantly increased at the ligated side. This increase was already observed on the first postoperative day, and maximal effects were reached on the 3rd day. We also observed a qualitative change in the scratching behaviour; postoperatively, scratching was often a vibratory-like shaking of the hind paw in the air. The time course of the increased scratching was time-locked with the development of allodynia to thermal stimulation. No differences were found either in the time course of the increased scratching behaviour or in the time course of the thermal allodynia between the rats ligated with resorbable and with non-resorbable sutures. However, a difference in the walking pattern, as measured by the sciatic functional index (SFI), was observed between the two groups: whereas the SFI normalized after 4 weeks in rats ligated with resorbable sutures, it remained disturbed until the end of the 16-week observation period in the rats ligated with non-resorbable sutures. Morphine 1, 2 and 5 mg/kg dose-dependently reduced the increased scratching behaviour. This was not due to a general depressant effect on the rats' behaviour. This finding is discussed in light of the debate on opioid sensitivity of neuropathic pain. The present results add new evidence that scratching is a possible sign of chronic pain in the animal.