[7] Tolerance, another condition that can arise from prolonged exposure to opioids, can often be mistaken for opioid-induced hyperalgesia and vice versa, as the clinical presentation can appear similar.
Although tolerance and opioid-induced hyperalgesia both result in a similar need for dose escalation to receive the same level of effect to treat pain, they are nevertheless caused by two distinct mechanisms.
[10] In addition, what appears to be opioid tolerance can be caused by opioid-induced hyperalgesia lowering the baseline pain level, thus masking the drug's analgesic effects.
[15] The pharmacology for opioid-induced hyperalgesia is more complicated, and is believed to involve the activation of NMDA receptors and increased excitatory peptide neurotransmitters (such as cholecystokinin).
[16] There is increasing evidence in support of genetics being a key factor in the development of OIH through its influence on both pain sensitivity and analgesic control.
This results in modulation of the dopaminergic and noradrenergic response at the synaptic level of neurons, which has been linked to having effects on memory function, anxiety, and pain sensitivity in comparison to individuals presenting as homozygous for valine alleles of this particular gene (COMTval158).
This information is important for healthcare professionals to know as it determines the dose of opioids a patient will need in order to achieve the desired analgesic effect.
Patients who are poor metabolizers should be given minimal amounts of opioids such as tramadol and codeine as they do not possess the necessary enzymes to turn it into its active metabolite desmetramadol.
[24] Studies on mice have shown silencing of the 6TM MOR variant decreased morphine-induced hyperalgesia which suggested G-protein coupling in the 6TM isoform could be a factor in the development of OIH.
[23][25] OIH shares commonalities with chronic pain in their neural mechanisms and specifically their usage of the glutaminergic system and NMDA glutamate receptors.
In the context of OIH, LTP has been shown to contribute to hyperalgesia by hypersensitizing areas of nociceptive processing, particularly at synapses between C fibers and the spinal cord dorsal horn.
Treatment of opioid tolerance and opioid-Induced hyperalgesia differs but it may be difficult to differentiate these two conditions in a clinical setting where most pain assessments are done through simple scale scores.
[32] One general treatment option is to gradually reduce or discontinue the dose of opioid to see if OIH is improved, although this could induce withdrawal symptoms that may initially increase pain.
[38] Opioid-induced hyperalgesia has also been criticized as overdiagnosed among chronic pain patients, due to poor differential practice in distinguishing it from the much more common phenomenon of opioid tolerance.
[39] The misdiagnosis of common opioid tolerance (OT) as opioid-induced hyperalgesia (OIH) can be problematic as the clinical actions suggested by each condition can be contrary to each other.