Unmasking the tonic-aversive state in neuropathic pain

Abstract

Tonic pain has been difficult to demonstrate in animals. Because relief of pain is rewarding, analgesic agents that are not rewarding in the absence of pain should become rewarding only when there is ongoing pain. We used conditioned place preference to concomitantly determine the presence of tonic pain in rats and the efficacy of agents that relieve it. This provides a new approach for investigating tonic pain in animals and for evaluating the analgesic effects of drugs.

Intrathecal reboxetine suppresses evoked and ongoing neuropathic pain behaviours by restoring spinal noradrenergic inhibitory tone

“…We show that intrathecal reboxetine acts to effectively suppress neuropathic sensitisation through an a2-mediated mechanism. Furthermore, we show that intrathecal reboxetine induces a place preference in nerve-injured (but not naive) animals, suggesting that it attenuates ongoing spontaneous pain, 27 whereas an equivalently effective antiallodynic dose of systemic reboxetine produces aversion in both tibial nerve transection (TNT) and naive animals.…”

“…We sought to gauge the effects of intrathecal and systemic reboxetine on "on-going" neuropathic pain using a conditioned place preference (CPP) paradigm 27,44 between days 21 to 25 post-TNT. Comparisons were made between TNT and naive rats receiving reboxetine either i.t.…”

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

“…Although stimulus response functions for escape from nociceptive stimuli can provide some comparable information from laboratory animals [66], assessment of "pain" requires reporting of the affective state associated with the altered sensation, and this has not been easy to accomplish in animals, including nonhuman primates. Recently, paradigms for assessing the aversive qualities of ongoing "painful" sensation have been reported for rodents [67], and these may be adapted to nonhuman primates after C7 hemisection to monitor the effects of therapies on recovery. Such an approach also could be used to evaluate whether current pharmacological strategies aimed at alleviating discomfort after SCI in nonhuman primates (e.g., the administration of gabapentin in response to skin lesions contralateral to the lesion) are actually affecting aversive sensation, yielding information that might be translated to the clinical arena.…”

The Analgesic Effects of (5R,6R)6-(3-Propylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1] Octane on a Mouse Model of Neuropathic Pain: Erratum

“…19,21,22 In brief, mice were preconditioned for 3 days, starting day 1 post-CPN ligation, and the chamber preference was evaluated on preconditioned day 3. The following day (day 4 post-CPN), mice received the appropriate control (ie, vehicle) paired with a randomly chosen chamber in the morning, and the appropriate drug treatment paired with the other chamber 4 hours later (afternoon).…”