Pleasure into pain: The consequences of long-term opioid use
Section snippets
Tolerance to opioid effects in methadone maintenance patients
People who are heroin dependent show marked tolerance to the effects of all opioid drugs. This is evident from the doses of heroin they typically administer; these doses would produce respiratory depression, vomiting, sedation, and possibly coma in a nontolerant person. When such people elect to participate in methadone maintenance programs, their tolerance and physical dependence are maintained but with a controlled, regular dosing regimen. Tolerance can be inferred where the effects of
Pain responses in methadone maintenance patients
One of the original measures used to evaluate opioid effects over the 24-h methadone dosing interval was response to pain produced by electrical stimulation. This produced results very similar to those described above for respiration; that is, methadone patients exhibited pronounced tolerance, but there was a residual analgesic effect of methadone at time of trough concentration with an increase in the effect at time of peak concentration (Dyer et al., 1999). Like the other measures, electrical
Hyperalgesia in methadone maintenance patients: cause and consequence
The evidence from our group and others that methadone patients are hyperalgesic to cold-pressor pain when compared to controls raises the issue of the generality of this phenomenon. Subsequent to the study reported above, we have observed hyperalgesia in patients maintained on buprenorphine (Compton, Charuvastra, & Ling, 2001) and slow-release oral morphine (Bochner, Mitchell, White, & Somogyi, 2003) and in heroin-dependent patients entering treatment (Ling et al., 2003). Hyperalgesia is
Mechanisms of opioid-induced hyperalgesia
In contrast to the model of tolerance and withdrawal presented in Fig. 1, pain responsiveness (as measured by the cold-pressor test in humans) is better represented by the model in Fig. 2. Here the adaptational response is of greater magnitude than the direct response to the drug so that there is a net decrease in response below baseline or control level. The term hyperadaptation may best describe adaptational responses that exceed the original drug response in magnitude.
The difference from
Mood states and withdrawal in methadone maintenance patients
In the case of pain, we have good evidence that the model of hyperadaptation fits the data and we also have potential mechanisms underlying the exaggerated drug-opposite response. If respiration, pupillary response, and electrical stimulation pain exhibit conventional tolerance, the question of the uniqueness or generality of the cold-pressor response arises. Does the hyperadaptation model apply to other drug effects or is it unique to certain kinds of pain response only and therefore of little
Implications for theory and practice
These findings have very important implications for understanding both the nature of dependence and the functional state of opioid-dependent people on admission to and during treatment. The suggestion that adaptation may be exaggerated for some responses leading to a drug-opposite or withdrawal-like state during drug administration is similar, in some respects, to the notion of hedonic homeostatic dysregulation. Koob and Le Moal (1997) characterized addiction in terms of a cycle of spiraling
Acknowledgements
Preparation of this paper was supported by NIDA grant RO1 DA 13706-01.
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