The importance of genetic background on pain behaviours and pharmacological sensitivity in the rat spared serve injury model of peripheral neuropathic pain.

Neuropathic pain conditions can encompass a diverse constellation of signs and symptoms consisting of sensory deficits, allodynia and hyperalgesia. Animal models of neuropathic pain have enabled the identification of key pathophysiological changes occurring within nociceptive pathways as a result of injury, and serve an invaluable role for preclinical screening of novel analgesic candidates. We have produced the first systematic description of the development and maintenance, and the pharmacological sensitivity of nociceptive behaviours in four rat strains with different genetic background (outbred Sprague-Dawley and inbred Brown Norway, Lewis and Fischer 344 rats), using the spared nerve injury model of peripheral neuropathic pain.

Amygdala GABA-A receptor involvement in mediating sensory-discriminative and affective-motivational pain responses in a rat model of peripheral nerve injury.

The contribution of the amygdala to neuropathic pain processing in animals has not been clearly acknowledged. To assess the relative contribution of amygdala GABA-A receptors in mediating sensory-discriminative and affective-motivational pain components, the GABA-A receptor agonist muscimol and the antagonist bicuculline (both 10-25 ng/microl) were administered by acute bilateral injection directly into the central amygdala in rats with a chronic constriction injury (CCI). Escape/avoidance behaviour reflecting the affective-motivational dimension of pain was measured using a light/dark chamber in combination with suprathreshold nociceptive stimulation, and was defined as a shift from the 'non-aversive' dark area of the chamber to the 'aversive' light area.

Venlafaxine compromises the antinociceptive actions of gabapentin in rat models of neuropathic and persistent pain.

Rationale: Neuropathic pain is associated with a number of disease states of diverse aetiology that can share common pathophysiological mechanisms. Antiepileptic drugs modulate ion channel function and antidepressants increase extracellular monoamine levels, and both drug classes variously attenuate signs and symptoms of neuropathic pain. Thus, coadministration of the antiepileptic gabapentin and the antidepressant venlafaxine may provide superior pain relief to administration of either drug alone.

Pharmacological characterisation of place escape/avoidance behaviour in the rat chronic constriction injury model of neuropathic pain.

Rationale: Classical pain tests performed in animals routinely measure evoked nociceptive behaviours. These almost exclusively reflect sensory processing of nociceptive transmission, although a recently described place escape/avoidance paradigm may be used to selectively assess affective pain processing.

Objective: To establish if drugs with proven analgesic efficacy selectively attenuate sensory-discriminative or affective-motivational aspects of nociceptive processing.

Activation of p38 and p42/44 MAP kinase in neuropathic pain: involvement of VPAC2 and NK2 receptors and mediation by spinal glia.

Activation of intracellular signaling pathways involving p38 and p42/44 MAP kinases may contribute importantly to synaptic plasticity underlying spinal neuronal sensitization. Inhibitors of p38 or p42/44 pathways moderately attenuated responses of dorsal horn neurons evoked by mustard oil but not brush and alleviated the behavioral reflex sensitization seen following nerve injury. Activation of p38 and p42/44 MAP kinases in spinal cord ipsilateral to constriction injury was reduced by antagonists of NMDA, VPAC2 and NK2 (but not related) receptors, the glial inhibitor propentofylline and inhibitors of TNF-alpha.