Whether dose increase happens during long term pain treatment with opioids depends on the opioid. The common mechanism for dose increase with morphine and simi

Whether dose increase happens during long term pain treatment with opioids depends on the opioid. The common mechanism for dose increase with morphine and similar opioids that act on mu-opiod receptors is their upregulation of NMDA receptors. NMDA upregulation increases pain sensitivity. Wash, rinse, repeat - the patient is on the dose escalation escalator. The opioid methadone is an NMDA antagonist (along with ketamine, memantine, and dextromethorphan, for example), making it much less likely to induce dose escalation when prescribed for otherwise intractable chronic pain. Methadone has a bad reputation because of 1) its association with treatment of heroin addiction and 2) its pharmacokinetics. The latter means that its blood concentration increase (and decrease, on cessation of the drug) changes slowly (think a week or so). When it's prescribed, it takes awhile to titrate for effect. If the process is rushed, it's possible to get lethal levels following several days after dose increase. It's basically a PID controller problem with a long phase lag between control input and effect. In a clinical setting that doesn't involve the difficulties of multiple drug abuse, it's a very useful medication for otherwise intractable chronic pain. Long way of saying that the opiate dose escalation issue is complicated.