Analgesic effects of loperamide in bone cancer pain in mice.
The intratibial inoculation of NCTC 2472 cells induces an osteosarcoma in C3H/HeJ mice. These mice show thermal hyperalgesic responses which may be blocked by the local administration of opiates over the tibial tumoral mass (Menéndez L, Lastra A, Hidalgo A, Meana A, Garcia E, Baamonde A. Peripheral opioids act as analgesics in bone cancer pain in mice. NeuroReport 2003b; 14:867-9). The aim of this report was to characterize the analgesic responses obtained by activating peripheral opioid receptors in bone cancer pain. Here, we initially describe that this osteosarcoma induces mechanical as well as thermal hyperalgesia. Loperamide, an opioid agonist unable to cross the blood-brain barrier, inhibits both thermal and mechanical hyperalgesia when s.c. injected, locally over the tibial tumoral mass (7.5-75 microg) or distantly, under the fur of the neck (4 mg/kg). These analgesic effects seem peripherally mediated since they are reverted by the administration of naloxone methiodide (10 mg/kg) and because the withdrawal latencies of the contralateral, non-affected, paws remain unaltered. Furthermore, only cyprodime (1 mg/kg) but not naltrindole (0.1 mg/kg) or nor-binaltorphimine (10 mg/kg) blocked these effects, showing the involvement of gamma-opioid receptors in the peripheral analgesia induced by loperamide on thermal and mechanical hyperalgesia. The advantages of using peripheral acting opiates -- devoid of central colateral effects -- for the treatment of cancer related pain are suggested.
Menéndez
Luis
L
Laboratorio de Farmacología, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Facultad de Medicina, Universidad de Oviedo, C/ Julián Clavería 6, 33006 Oviedo, Asturias, Spain. luismen@uniovi.es
Lastra
Ana
A
Meana
Alvaro
A
Hidalgo
Agustín
A
Baamonde
Ana
A
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D008139:Loperamide / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D000700:Analgesics; D008139:Loperamide