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.
Crisp
Terriann
T
Department of Physiology and Pharmacology, Des Moines University, Des Moines, IA 50312-4198, USA. Terriann.Crisp@dmu.edu
Minus
Timothy O
TO
Coleman
Michelle L
ML
Giles
Jennifer R
JR
Cibula
Charles
C
Finnerty
Edward P
EP
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000517:prevention & control*; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000975:Antioxidants; D011281:Pregnatrienes; C053355:tirilazad