Opioid induced hyperalgesia

In addition to the development of tolerance, persistent administration of opioid analgesics has been observed to increase the sensation of pain leading to a state of hyperalgesia. This phenomenon has been observed with several opioid analgesics, including morphine, fentanyl, and remifentanil. Spinal dynorphin and activation of the bradykinin receptor have emerged as important candidates for the mediation of opioid-induced hyperalgesia. 

Angst MS, Clark JD Opioid-induced hyperalgesia. Anesthesiology 2006 104 570. [PMID 16508405]... 

Chu LF, Angst MS, Clark D Opioid-induced hyperalgesia in humans Molecular mechanisms and clinical considerations. 

King T et al Role of NK-1 neurotransmission in opioid-induced hyperalgesia. Pain 2005 116 276. [PMID 15964684]... 

A second clinical alteration observed in patients treated with opioids is termed opioid induced hyperalgesia [11]. This phenomenon is characterized by paradoxical increases in pain intensity (hyperesthesia), the development of new pain complaints, and alterations in pain characteristics (allodynia) in response to continued administration or increased dosing of opioid analgesics. 

Hyperalgesia infusions of remifentanil have been associated with acute tolerance development and opioid-induced hyperalgesia. Both factors can increase post-operative opioid dose requirements and increase pain intensity scores [4]. 

Chu LF, Clark D, Angst MS. Molecular basis and clinical implications of opioid tolerance and opioid-induced hyperalgesia. In Sinatra RS, de Leon-Casasola OA, Ginsberg B, Viscusi ER, eds. Acute Pain Management. New York Cambridge University Press,... 

Table 38.1. Opioid tolerance versus opioid-induced hyperalgesia (OiH)...

Recognition of the phenomenon of opioid-induced hyperalgesia in the clinical setting is the foremost... 

Figure 38.1. Clinical algorithm for differentiating worsening pain states despite continuation of opioid therapy. (Reprinted with permission from Mitra S. Opioid-induced hyperalgesia pathophysiology and clinical implications. J Opioid Manage 2008 4 123-130.)...

Mitra S. Opioid-induced hyperalgesia pathophysiology and clinical implications. / Opioid Manage 2008 4 123-130. 

Koppert W, Schmelz M. The impact of opioid-induced hyperalgesia for postoperative pain. Best Pract Res Clin Anaesthesiol 2007 21 65-83. 

Ziconotide provides powerful and prolonged analgesia for patients suffering chronic intractable pain that is poorly responsive to conventional opioid and nonopioid analgesics. An important advantage of ziconotide is the avoidance of opioid-induced adverse events such as GI issues, pruritus, decreased testosterone levels, opioid-induced hyperalgesia, as well as behavioral issues. 

There are no RCTs of nicotine for chronic nonmalignancy pain or cancer pain. The existing data suggest that chronic nicotine users may actually be more sensitive to pain than non-smokers. Symptoms are more pronounced in smokers with more severe nicotine dependence [6]. The association between the intensity of pain in chronic pain states and smoking status was explained by higher levels of substance P (P for pain) in the cerebral spinal fluid and lower plasma beta-endorphin levels than in non-smokers. There are similarities between hypersensitivity to pain induced by chronic nicotine use and opioid-induced hyperalgesia and opioid-induced tolerance in chronic pain states. Further research is needed to explore and explain these effects. 

Pharmacological tolerance of analgesic effects, symptoms of withdrawal, opioid-induced hyperalgesia, and psychological factors have been reported as contributing... 

Chu LF, D Arcy N, Brady C, Zamora AK, Young CA, KimJE, et al. Analgesic tolerance without demonstrable opioid-induced hyperalgesia a double-blinded, randomized, placebo-controUed trial of sustained-release morphine for treatment of chronic nonradicular low-back pain. Pain August 2012 153(8) 1583-92. 

In contrast to the analgesic role of leu- and met-enkephalin, an analgesic action of dynorphin A—through its binding to (kappa) opioid receptors—remains controversial. Dynorphin A is also found in the dorsal horn of the spinal cord, where it may play a critical role in the sensitization of nociceptive neurotransmission. Increased levels of dynorphin can be found in the dorsal horn after tissue injury and inflammation. This elevated dynorphin level is proposed to increase pain and induce a state of long-lasting hyperalgesia. The pronociceptive action of dynorphin in the spinal cord appears to be independent of the opioid receptor system but dependent on the activation of the bradykinin receptor. Moreover, dynorphin A can bind and activate the N -methyl-D-aspartate (NMDA) receptor complex, a site of action that is the focus of intense therapeutic development. 

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