Opiate tolerance to daily heroin administration: an apparent phenomenon associated with enhanced pain sensitivity.
From a classical viewpoint, tolerance to analgesic effects of opiates refers to the decreased effectiveness of a given opiate following its repeated use. Despite much research, it has not been conclusively demonstrated in vivo that functional changes observed at the opioid receptor level in the responsiveness to opiates account for development of tolerance. An alternative hypothesis is that opioid receptors remain operative following repeated opiate administration but that opioid receptor activation rapidly induces a prolonged increase in pain sensitivity which opposes the predominant opiate analgesic effect following repeated opiate administration. We recently showed that a single heroin administration induces an enhanced pain sensitivity for several days, a phenomenon which is prevented by the non-competitive N-methyl-D aspartate receptor antagonist MK-801. Herein we report that repeated once-daily heroin injections induced a gradual lowering of the nociceptive threshold which progressively masked a sustained heroin analgesic functional effect. MK-801 prevented such opiate-induced allodynia and thereby prevented development of an apparent decrease in the effectiveness of heroin. These results indicate that intermittent heroin administration induced a persistent increase in the basal pain sensitivity which, if not taken into account gives the impression of less analgesia, i.e. apparent tolerance.
Laulin
J P
JP
INSERM U 259, Bordeaux, France.
Célèrier
E
E
Larcher
A
A
Le Moal
M
M
Simonnet
G
G
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005528:Foot; D003932:Heroin / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008297:Male; D017288:Pain Threshold / Q000187:drug effects*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D014828:Vocalization, Animal
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003932:Heroin