TY - JOUR
T1 - Antihyperalgesic effects of loperamide in a model of rat neuropathic pain are mediated by peripheral δ-opioid receptors
AU - Shinoda, Katsumi
AU - Hruby, Victor J.
AU - Porreca, Frank
PY - 2007/1/10
Y1 - 2007/1/10
N2 - The possible antihyperalgesic and antiallodynic activity of loperamide, an opioid agonist which does not readily penetrate the blood-brain barrier, were examined in the spinal nerve ligation model of experimental neuropathic pain. Intraperitoneal (i.p.) injection of loperamide effectively reversed thermal hyperalgesia. In contrast, loperamide had minimal effects on cold allodynia and no effects on mechanical allodynia. The antihyperalgesic action of loperamide against noxious heat was antagonized by naltrindole, a δ-opioid receptor selective antagonist, but not by pretreatment with β-funaltrexamine, a μ-opioid receptor selective antagonist, or administration of nor-binaltorphimine, a κ-opioid receptor selective antagonist. Furthermore, i.p. injection of [d-Ala2, Glu4]-deltorphin II, a δ-opioid receptor selective peptide agonist, also reversed thermal hyperalgesia. The present results suggest that thermal hyperalgesia in experimental neuropathic pain can be reduced through activation of peripheral δ-opioid receptors. The data suggest the possible application of peripherally restricted and δ-opioid receptor selective agonists in the treatment of some aspects of neuropathic pain without many of the side effects associated with centrally acting opioids and without the peripheral side effects of opioid agonists acting at μ-receptors.
AB - The possible antihyperalgesic and antiallodynic activity of loperamide, an opioid agonist which does not readily penetrate the blood-brain barrier, were examined in the spinal nerve ligation model of experimental neuropathic pain. Intraperitoneal (i.p.) injection of loperamide effectively reversed thermal hyperalgesia. In contrast, loperamide had minimal effects on cold allodynia and no effects on mechanical allodynia. The antihyperalgesic action of loperamide against noxious heat was antagonized by naltrindole, a δ-opioid receptor selective antagonist, but not by pretreatment with β-funaltrexamine, a μ-opioid receptor selective antagonist, or administration of nor-binaltorphimine, a κ-opioid receptor selective antagonist. Furthermore, i.p. injection of [d-Ala2, Glu4]-deltorphin II, a δ-opioid receptor selective peptide agonist, also reversed thermal hyperalgesia. The present results suggest that thermal hyperalgesia in experimental neuropathic pain can be reduced through activation of peripheral δ-opioid receptors. The data suggest the possible application of peripherally restricted and δ-opioid receptor selective agonists in the treatment of some aspects of neuropathic pain without many of the side effects associated with centrally acting opioids and without the peripheral side effects of opioid agonists acting at μ-receptors.
KW - Loperamide
KW - Neuropathic pain
KW - Peripheral δ-opioid receptors
KW - Thermal hyperalgesia
UR - http://www.scopus.com/inward/record.url?scp=33751417924&partnerID=8YFLogxK
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U2 - 10.1016/j.neulet.2006.10.027
DO - 10.1016/j.neulet.2006.10.027
M3 - Article
C2 - 17110034
AN - SCOPUS:33751417924
SN - 0304-3940
VL - 411
SP - 143
EP - 146
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -