The Influence of Aging and Duration of Nerve Injury on the Antiallodynic Efficacy of Analgesics in Laboratory Mice

Introduction: Increasing attention is being paid to the effects of organismic factors like age on pain sensitivity. However, very little data exist on this topic using modern algesiometric assays and measures in laboratory rodents.

Objectives: We investigated the effect of age and duration of nerve injury on baseline mechanical thresholds, neuropathic allodynia, and the antiallodynic and analgesic efficacy of 4 systemically administered analgesics: amitriptyline, diclofenac, morphine, and pregabalin.

Methods: Mice of both sexes and 3 conditions were compared: Young-Young, in which baseline testing (von Frey thresholds), the injury producing neuropathic pain (spared nerve injury [SNI]) and subsequent drug testing occurred while mice were young (8-10 weeks); Young-Old, in which mice received the nerve injury while young but were tested for drug efficacy over 10 months later; and Old-Old, in which both the nerve injury and drug testing occurred at approximately 1 year of age.

Results: Old-Old mice were found to display higher baseline mechanical sensitivity than other groups. No group differences were seen in SNI-induced allodynia in males; female Young-Old mice were found to display greatly reduced allodynia. With respect to drug efficacy, no differences among conditions were observed for amitriptyline, diclofenac, or morphine. For pregabalin, however, Young-Old mice displayed significantly reduced antiallodynia, and the drug was completely ineffective in Old-Old mice.

Conclusion: Novel findings include the apparent remission of SNI-induced allodynia in female mice 10 months after injury and reduced pregabalin antiallodynic effects produced by both the passage of time after nerve injury and aging.