Involvement of Selective Alpha-2 Adrenoreceptor in Sympathetically Maintained Pain

Abstract

Objective : Peripheral nerve injury often leads to neuropathic pain, which is characterized by burning pain, allodynia, and hyperalgesia. The role of the sympathetic nervous system in neuropathic pain is a complex and controversial issue. It is generally accepted that the alpha adrenoreceptor (AR) in sympathetic nerve system plays a significant role in the maintenance of pain. Among alpha adrenoreceptor, alpha-1 receptors play a major role in the sympathetic mediated pain. The primary goal of this study is to test the hypothesis that sympathetically maintained pain involves peripheral alpha-2 receptors in human. Methods : The study was a randomized, prospective, double-blinded, crossover study involving twenty patients. The treatments were : Yohimbine (30 mg mixed in 500 mL normal saline), and Phentolamine (1 mg/kg in 500 mL normal saline) in 500 mL normal saline at 70 mL/hr initially then titrated. The patients underwent infusions on three different appointments, at least one month apart. Thus, all patients received all 2 treatments. Pain measurement was by visual analogue scale, neuropathic pain questionnaire, and McGill pain questionnaire. Results : There were significant decreases in the visual analogue scale, neuropathic score, McGill pain score of yohimnine, and phentolamine. Conclusion : We conclude that alpha-2 adrenoreceptor, along with alpha-2 adrenoreceptor, may be play role in sympathetically maintained pain in human. KEY WORDS :Reflex sympathetic dystrophy˙ Yohimbine˙ Alpha-2 antagonist.

Use of sensory-sympathetic coupling indices for diagnosing sympathetically maintained pain with laser Doppler flowmetry

“…After intracutaneous injection of norepi nephrine, the pain and hyperalgesia that had been relieved after sympathectomy or sympathetic block came back [15]. Later, it was demonstrated that not only predominantly the α 1 adrenoreceptors [5,16,17] but also the α 2 adrenoreceptors [18] played a role in sympathetically maintained pain on the periphery. β Adrenergic blockade with propranolol slightly influ enced sympathetically maintained pain [7].…”

Chemoreactomic analysis of citrulline malate molecules

“…Ингибирование адренергических [25,26] и глутаматных рецепторов на фоне стимулирования дофаминовой [27] и серотониновой [28] активности может способствовать формированию анальгетического эффекта. Действительно, моделирование экспериментальных неврологических эффектов цитруллина подтверждает этот вывод: по сравнению с контрольными молекулами цитруллин характеризовался более выраженным анальгетическим действием (см.…”

Janus Molecule I: Dichotomous Effects of COMT in Neuropathic vs Nociceptive Pain Modalities

“…Intravenous administration of phentolamine suppresses nociceptor excitation, which is blocked by the selective α 1 - antagonist prazosin [147]. In human trials, patients with sympathetically maintained pain (SMP) report reduced thermal and mechanical sensitivity following the intravenous administration of phentolamine [148]; however significant analgesia in response to intravenously administered phentolamine was not observed in a later SMP clinical trail [149] or in a painful diabetic neuropathy trail [150]. Furthermore, the subcutaneous administration of the nonselective α-antagonist RS42206 has no effect on thermal or mechanical sensitivity in sciatic nerve transected mice [151].…”

“…However, it has been also reported that the α 2 -antagonist yohimbine produces analgesia in neuropathic pain patients [149]. It is not clear if the analgesic effects of yohimbine are mediated by blocking α 2 -receptors because this compound also has effects on serotonin receptors [116–118] and thus the observed analgesic effects could be mediated by receptors other than α 2 -adrenergic receptors.…”