BACKGROUND: Opioids have long been regarded as the most effective drugs for the treatment of severe acute and @entity1118 . Unfortunately, their therapeutic efficacy and clinical utility have been limited because of central and peripheral side effects. METHODS: To determine the therapeutic value of peripheral  -opioid receptors as a target for @entity9 treatment, the authors examined the effects of dermorphin [D- @entity39573 , Lys4] (1-4) @entity6346 ( @entity69972 ), a hydrophilic, peripherally acting  -opioid receptor agonist, in male and female @entity35 with spinal nerve ligation-induced @entity9 . The authors also utilized behavioral, pharmacologic, electrophysiologic, and molecular biologic tools to characterize @entity69972 's possible mechanisms of action in male @entity35 . RESULTS: @entity69972 , administered subcutaneously, had 70 times greater efficacy for inhibiting thermal (n = 8 to 11/group) than mechanical @entity56 (n = 6 to 8/group) in male @entity35 . The @entity158 inhibitory effects of @entity69972 on mechanical and @entity56 were abolished in animals pretreated with systemic @entity25716 (n = 7 to 9/group), a peripheral  -opioid receptor antagonist. In the spinal wide-dynamic range neurons, systemic @entity69972 inhibited @entity7183 -mediated, but not A-fiber-mediated, response in neuropathic male @entity35 (n = 13). In primary sensory neurons, @entity69972 inhibited the @entity2951 -induced [ @entity141 ] increase more than the @entity9882 -induced [ @entity9495 ] increase (n = 300); @entity2951 and @entity9882 activate subpopulations of neurons involved in the signaling of heat and @entity158 , respectively. @entity69972 -treated @entity35 (n = 5 to 8/group) did not exhibit motor @entity73 suggesting that it does not induce central side effects. CONCLUSIONS: These findings suggest that @entity69972 may represent a potential alternative to current opioid therapy for the treatment of @entity9 and is likely to be associated with minimal adverse effects.

Activation of Peripheral  -opioid Receptors by Dermorphin [D- @entity39573 , Lys4] (1-4) XXXX Leads to Modality-preferred Inhibition of @entity9 .

@entity2951 :: ('MESH:D002211', 'Chemical') :: ['capsaicin'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+'] @entity39573 :: ('29215(Tax:10116)', 'Gene') :: ['Arg2'] @entity9882 :: ('MESH:D000861', 'Chemical') :: ['b-alanine'] @entity9495 :: ('D002118', 'Chemical') :: ['Ca'] @entity73 :: ('MESH:D003072', 'Disease') :: ['deficits and locomotor impairment'] @entity25716 :: ('MESH:C032257', 'Chemical') :: ['methylnaltrexone'] @entity7183 :: ('10185', 'Species') :: ['C-fiber'] @entity56 :: ('MESH:D004342', 'Disease') :: ['hypersensitivity', 'heat hypersensitivity'] @entity69972 :: ('MESH:C063076', 'Chemical') :: ['DALDA'] @entity158 :: ('MESH:D010146', 'Disease') :: ['mechanical pain', 'pain'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity6346 :: ('CHEBI:32988', 'Chemical') :: ['amide'] @entity1118 :: ('MESH:D059350', 'Disease') :: ['chronic pain'] @entity9 :: ('MESH:D009437', 'Disease') :: ['neuropathic pain']
@entity6346 :: (CHEBI:32988,Chemical) :: ['Amide']
