What Do We Know About Opioid-Induced Hyperalgesia?

Second, OIH would possibly exacerbate a pre-existing pain condition. Overall pain intensity (VAS) would be conceivably increased above the level of pre-existing pain in the absence of disease progression. Opioid dose escalation could only transiently and minimally reduce pain intensity in such a setting, with a subsequent increase in pain intensity due to OIH.

Third, when a diagnosis is uncertain, a trial of opioid dose escalation or tapering may be helpful to differentiate between tolerance and OIH. In an undertreated, worsening pain condition due to disease progress and/or pharma-cologic opioid tolerance, improved pain control may well be seen after a trial of opioid dose escalation. On the other hand, opioid dose escalation may exacerbate pain due to OIH, while a supervised opioid tapering may reduce OIH and improve clinical pain management. In this regard, if a patient is on a low opioid dose regimen and complains of unsatisfactory pain relief, a trial of opioid dose escalation may be appropriate; if a patient is already on a high dose of opioid analgesics, further dose escalation is rarely justified and may exacerbate OIH.

It is important to remember that the clinical outcome of opioid therapy is a dynamic balance among the opioid analgesic effect, OIH, and worsening pain due to disease progression. While any opioid dose escalation may transiently increase the analgesic effect, albeit by a small degree in many cases, the real issue is whether the same dose escalation may also exacerbate OIH, which could quickly overtake the transient increase in the opioid analgesic effect. Therefore, clinical judgment is fundamentally important and all clinical conditions related to opioid therapy need to be taken into consideration in the decision making process.

Summary

Interest in understanding OIH has grown over the last decade. Many discussions and reviews have centered around several key issues: (1) opioids not only produce analgesia through their anti-nociceptive effect, but also induce hyperalgesia via a pro-nociceptive effect; (2) opioid tolerance itself may be part of sensitization of a pro-nociceptive process; (3) the onset of OIH may be later than that of opioid tolerance and OIH may be a dose-related process, although OIH has been reported following acute and chronic opioid exposure at both high and low doses; (4) it is unclear whether a certain type of opioid and route of administration may be more likely to lead to clinical presentation of OIH; and (5) although opioid tolerance, OIH, and opioid withdrawal may share some common factors and mechanisms, the mechanism underlying each of these phenomena remains unclear [83].

While OIH has been well documented and investigated over nearly 2 decades, its exact clinical characteristics and underlying mechanisms have yet to be fully determined [84]. In addition, opioid tolerance should be differentiated from OIH, although both have a similar clinical presentation with regard to change in pain intensity [85]. Clinically, OIH should be considered when the adjustment of opioid dose is contemplated if prior opioid dose escalation fails to provide the expected analgesic effect and there is unexplainable pain exacerbation following an initial period of effective opioid analgesia. Although in some cases increasing opioid dose leads to some improvement in pain management, in other cases less opioid may be more effective in pain reduction. This goal may be accomplished by initiating a trial of opioid tapering, opioid rotation, adding adjunctive medications, or combining opioid with a clinically available NMDA receptor antagonist. Continuing opioid therapy with endless dose escalation in the absence of clinical evidence of improved pain management is neither scientifically sound nor clinically justified.