Aging, peripheral nerve injury and nociception: effects of the antioxidant 16-desmethyltirilazad.

Peripheral neuropathies increase with aging, and reactive oxygen species contribute to the symptomatology of neuropathic pain disorders. In this study, we examined age-related differences in the therapeutic efficacy of pre- or post-treatments of the amino-steroidal antioxidant 16-desmethyltirilazad in delaying the onset and/or limiting the duration of tactile-evoked allodynia following the induction of peripheral mononeuropathies in rats. Two different models of nerve injury were utilized to induce allodynia in young and aged rats: (1) the chronic constriction injury (CCI) model of Bennett and Xie [Bennett GJ, Xie Y-K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33:87-107]; (2) the partial sciatic nerve ligation (PSNL) model of Seltzer et al. [Seltzer Z, Dubner R, Shir YA. Novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain 1990;43:205-18]. Calibrated von Frey filaments were used to examine changes in paw withdrawal threshold values. The results demonstrated that pre-treating young and aged rats with 16-desmethyltirilazad prior to the induction of peripheral mononeuropathies prevented the onset of neuropathic pain. However, once post-operative tactile allodynia was established, post-treatment therapy was ineffective at reversing the symptoms. These findings support the mediatory role of reactive oxygen species in neuropathic pain disorders, and suggest that the antiallodynic efficacy of antioxidant intervention is dependent on the time course of administration.

The effects of aging on thermal hyperalgesia and tactile-evoked allodynia using two models of peripheral mononeuropathy in the rat.

The effects of aging on the behavioral manifestations of neuropathic and inflammatory pain were investigated using two models of peripheral nerve injury. The left sciatic nerve of young and aged Fischer 344 FBNF1 hybrid rats (4-6 and 24-26 months old, respectively) was ligated using either the chronic constriction injury (CCI) model of Bennett and Xie or the partial sciatic nerve ligation (PSNL) model of Seltzer et al. A plantar analgesic meter was used to assess age-related differences in CCI- or PSNL-induced thermal hyperalgesia, and nerve injury-induced tactile-evoked allodynia was assessed with von Frey filaments. Aged animals subjected to the PSNL procedure developed a more vigorous and longer lasting thermal hyperalgesic response than did aged rats post-CCI. The CCI model incorporates a more prominent peripheral inflammatory component than the PSNL model. These data support the notion that the peripheral inflammatory response is diminished in aged rats.