Clinical Review

What Do We Know About Opioid-Induced Hyperalgesia?

Journal of Clinical Outcomes Management. 2014 April;21(4)

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Opioid Regimen and OIH

Opioid regimen features, including type of opioid and dose, may influence the development of OIH. Anecdotal clinical observations have suggested that degree of OIH may vary according to opioid regimen [75]. Although the exact relationship between the dose regimen and the development of OIH remains to be determined, it is conceivable that OIH would be more likely to develop in patients receiving high opioid doses with a prolonged treatment course, although OIH has been demonstrated in patients receiving a short course of highly potent opioid analgesics [76]. Moreover, patients with a pathological pain condition (eg, neuropathic pain) treated with opioid therapy may be more susceptible to developing opioid-induced pain, because both pathological pain and OIH may share a common cellular mechanism [77].

If OIH develops following exposure to one opioid, can switching to a different opioid diminish OIH [78]?If cross-pain sensitivity does not develop between different opioids, switching to a different opioid would be justified, a similar rationale to that for opioid rotation to overcome opioid tolerance. This issue remains to be addressed.

OIH and Pre-emptive Analgesia

There is an ongoing debate about the clinical effectiveness of pre-emptive analgesia in pain management. However, use of opioid analgesic as the sole agent for pre-emptive analgesia may not be desirable for several reasons. First, a large dose of intra-operative opioids could activate a pro-nociceptive mechanism leading to the development of postoperative OIH [79]. This may confound the assessment of postoperative pain and counteract the opioid analgesic effect. Second, pre-emptive analgesia calls for pre-emptive inhibition of neuroplastic changes mediated through multiple cellular mechanisms such as the central glutamatergic system. Paradoxically, opioid administration could activate the central glutamatergic system as discussed above. Third, the neural mechanism of opioid tolerance and OIH may interact with that of pathological pain and pathological pain could be exacerbated following opioid administration [80,81]. This issue needs to be investigated in future studies.

Clinical Implications and Management of OIH

Until recently, a decreased opioid analgesic effect associated with opioid therapy was often recognized as the presence of pharmacologic opioid tolerance (ie, desensitization of the responsiveness of the opioid receptor and its cellular mechanism) and/or a worsening of the clinical pain condition. Therefore, opioid dose escalation appeared to be a logical approach to regain analgesic effectiveness. This practice should be reconsidered in light of the information on OIH. In the clinical setting, apparent opioid tolerance may result from pharmacological tolerance, worsening pain condition due to disease progression, and/or OIH. Below are some factors to consider in forming a differential diagnosis in the clinical setting [82].

First, the quality, location, and distribution pattern of the pain related to OIH would be different from a pre-existing pain condition. Because opioid analgesics are often administered systemically, changes in pain quality would be diffuse as compared with the pre-existing pain condition. Since the mechanism of OIH is similar to that of pathological pain, such as neuropathic pain, changes in pain threshold, tolerability, and distribution patterns seen in OIH would be similar to those seen in neuropathic pain patients. Quantitative sensory testing may be a useful tool to detect such changes.