THE RESOLUTION OF NEUROPATHIC HYPERALGESIA FOLLOWING MOTOR AND SENSORY FUNCTIONAL RECOVERY IN SCIATIC AXONOTMETIC MONONEUROPATHIES

Nerve lesions producing extensive axonal loss can induce painful hyper algesic states in man. The affect of axonal regeneration and end-organ reinnervation on hyperalgesia and pain is controversial. This study u sed two axonotmetic models, the sciatic crush injury (CI) and the scia tic chronic constrictive injury (CCI), to investigate the affects of n erve regeneration and reinnervation on hyperalgesia and presumed painf ul behavior in rats. The sciatic Cf resulted in a transient loss of bo th sciatic motor function and the withdrawal response to pinch and hea t in the sciatic distribution. Extensive recovery of motor function, p inch and heat response occurred over days 23-38 post-crush injury. Thi s temporally corresponded with a plateau in the hindpaw autotomy score and a resolution of the saphenous-mediated pressure and heat hyperalg esia (adjacent neuropathic hyperalgesia; ANH) which developed over the medial dorsum of the hindpaw following the sciatic CI. In contrast, w ith sciatic transection and distal stump excision, no motor recovery o ccurs, large areas of the hindpaw remain unresponsive to heat and pinc h, and the saphenous mediated ANH fails to resolve over a period of 3 months. When sciatic CI was compared to contralateral sciatic transect ion within the same rat, the bilateral saphenous-mediated pressure and heat thresholds were initially identical, but by 23-27 days post-crus h, the crush side thresholds became hypoalgesic relative to the sectio n side. This demonstrates an attenuation of the crush-induced ANH-whic h temporally corresponds to the recovery of motor and sensory function . When the sciatic nerve was proximally crushed and distally transecte d (3 cm below the crush site), the saphenous-mediated pressure and hea t threshold changes were identical (over 6 weeks of serial testing) to those produced by a contralateral sciatic transection within the same rat. This indicates that the microenvironments surrounding the regene rating axon tips did not differentially affect the development of ANH following sciatic CI or transection. The sciatic CCI resulted in a tra nsient loss of hindpaw motor function without the loss of pinch or hea t withdrawal responses in the sciatic distribution. Motor function rec overy occurred primarily over days 23-59 post-ligature. During this pr olonged period of motor function recovery there was a resolution of th e sciatic-mediated plantar surface heat hyperalgesia and the saphenous -mediated heat ANH. The above data support the hypothesis that the suc cessful regeneration of distal axons after axonotmetic lesions can ini tiate the resolution of neuropathic hyperalgesia.