Effects of loperamide on mechanical allodynia induced by herpes simplex virus type-1 in mice.
In the present study, we investigated whether the peripherally acting micro-opioid receptor agonist loperamide would inhibit allodynia in the non-inflamed dermatome of mice with herpetic pain. Subcutaneous (s.c.) injection of loperamide (1 and 3 mg/kg) inhibited allodynia. Local (intraplantar) injection of loperamide (1 and 5 microg/site) also produced an anti-allodynic effect. The peripheral opioid receptor antagonist naloxone methiodide (0.1 mg/kg, s.c.) and the micro-opioid receptor-selective antagonist beta-funaltrexamine (40 nmol/site, intraplantar and 20 mg /kg, s.c.) antagonized the anti-allodynic effects of systemic and local loperamide. Local injection of loperamide into the contralateral hind paw was without effect, suggesting that the effect is mediated through local action, not systemic action. Acute and subacute tolerance did not develop to the anti-allodynic effect of loperamide. In addition, there were no cross-tolerance between local opioids (morphine and loperamide) and systemic morphine. These results suggest that stimulation of peripheral micro-opioid receptors suppresses herpetic allodynia without tolerance development. The non-narcotic micro-opioid receptor agonist loperamide may relieve acute herpetic pain in patients with herpes zoster.
Sasaki
Atsushi
A
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Nakashima
Yasutaka
Y
Takasaki
Ichiro
I
Andoh
Tsugunobu
T
Shiraki
Kimiyasu
K
Kuraishi
Yasushi
Y
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D000818:Animals; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D005528:Foot; D006561:Herpes Simplex / Q000150:complications*; D018259:Herpesvirus 1, Human; D007267:Injections; D007279:Injections, Subcutaneous; D008139:Loperamide / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology*; D010812:Physical Stimulation
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009271:Naltrexone; D008139:Loperamide; C024524:beta-funaltrexamine; D009020:Morphine