In certain patients with neuropathic pain, the pain and hyperalgesia are dependent on sympathetic innervation of the painful area (sympathetically maintained pain, SMP). We recently determined in patients with SMP that phentolamine, a short-acting alpha-adrenergic antagonist, reduces the pain associated with SMP. Clonidine, an alpha-2 adrenergic agonist, reduces hyperalgesia in the area of application when applied topically in patients with SMP. We postulate that in SMP alpha-1 adrenergic sensitivity develops in nociceptors such that the release of norepinephrine from the sympathetic terminals activates the nociceptors and leads to pain. In this proposal, we plan to test this hypothesis by performing neurophysiological studies of single, identified nociceptors in anesthetized monkey following establishment of a controlled nerve injury induced by applying a tight ligature applied to a single, lumbar spinal nerve. This controlled nerve injury has been demonstrated to produced hyperalgesia to heat, cold, and mechanical stimuli in monkey. Our preliminary studies indicate nociceptors exhibit adrenergic sensitivity following this nerve injury. Specifically, we aim to answer the following questions: How are the response properties of cutaneous nociceptors to controlled thermal and mechanical stimuli altered by the nerve injury? Do cutaneous nociceptors develop adrenergic sensitivity, and does this sensitivity lead to alterations in response to natural stimuli? What adrenergic receptor subclasses are involved? Using standard teased-fiber recording techniques, we will measure the response of single nociceptors evoked by intra-arterial administration of selective adrenergic agonists and blocked by intradermal administration of selective adrenergic antagonists. These studies will further our understanding of the physiology and pharmacology of neuropathic pain and should lead to improved methods of diagnosing and treating this disease.
| Clark, M R; Heinberg, L J; Haythornthwaite, J A et al. (2000) Psychiatric symptoms and distress differ between patients with postherpetic neuralgia and peripheral vestibular disease. J Psychosom Res 48:51-7 |
