The development of chronic mechanical hyperalgesia, autotomy and collateral sprouting following sciatic nerve section in rat

Abstract

The development of mechanical hyperalgesia over the tarsometatarsal joints subsequent to chronic sciatic section was studied in rats. Mechanical thresholds began to drop within 7 days of sciatic section and continued to decline for 2–3 weeks, resulting in significant hyperalgesia over the original saphenous and sciatic border zones lasting up to 310 days. Contralateral hyperalgesia, which is seen in tissue injury mechanical hyperalgesia, failed to develop. Collateral sprouting of high-threshold mechanoreceptors from the saphenous nerve into the denervated deep and cutaneous tissue was observed. The extent of cutaneous sprouting did not significantly correlate with the severity of hyperalgesia. The simultaneous uniform reduction of mechanical thresholds across all tarsometatarsal areas after chronic sciatic section is consistent with a central modulation of nociceptive afferent input. The severity and temporal development of the hyperalgesia strongly correlated with the extent of autotomy behavior. This animal model of chronic mechanical hyperalgesia following peripheral nerve section closely resembles a human neuropathic pain syndrome and may provide an experimental opportunity to advance our understanding of the neuropathology subserving chronic pain.