User:NavkiranSandhu/sandbox

Treatment of opioid tolerance and Opioid-Induced Hyperalgesia (OIH) 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. The treatment for OIH may be challenging because of the lack of adequate quality studies published, which is possibly due to the complexity in diagnosis of OIH and challenges in working with patients on chronic opioids. Currently there is no single best pharmacologic treatment for OIH and clinicians are advised to choose an appropriate therapy based on the unique clinical scenario and history of each patient.

One general treatment option is to reduce or discontinue the dose of opioid to see if OIH is improved, although this could induce withdrawal symptoms that may initially increase pain.[16] Opioid sparing or opioid switching, which refers to the replacement of the current opioid with another pharmacological agent such as morphine or methadone, has been reported to be effective in some studies but this may also increase the sensitivity to pain according to some case reports , requiring higher doses of the opioid sparing drug.[8] Ketamine, an NMDA antagonist, has been shown to prevent the extended use of opioid in post-operative hyperalgesia when it is infused in a small amount perioperatively along with the opioid but there are also studies that show ketamine being ineffective in modulating hyperalgesia. Methadone is also believed to show some efficacy in OIH, presumably due to its weak NMDA antagonist activity.[16] The use of an NSAID, especially some COX-2 inhibitors, or acetaminophen either as monotherapy or combination therapy [17] is also suggested as a possible treatment option. '''a2 agonists, such as Clonidine and Dexmedetomidine, have been studied as alternatives or adjuncts to opioids for their analgesic properties in the perioperative setting.[20] They have been shown to decrease the need for opioids after surgery, which may reduce the risk of hyperalgesic effects associated with prolonged opioid use. However, there is currently insufficient data to support the clinical effectiveness of a2 agonists in reducing postoperative OIH.[20] Mesenchymal stem cell (MSC) therapy has shown efficacy in the prevention and treatment of OIH in animal studies.[4] Palmitoylethanolamide (PEA) has been studied for it's anti-inflammatory and analgesic effects and emerging data suggests that it may have a role in delaying the onset of opioid tolerance and reducing the development of OIH when used in conjunction with opioids.[5]'''

1. Opioid-induced hyperalgesia: a review of epidemiology, mechanisms and management. Yinghui Low, Collin F. Clarke, Billy K. Huh Singapore Med J. 2012 May; 53(5): 357–360. PMID: 22584979

2. Peter Yi, Peter Pryzbylkowski; Opioid Induced Hyperalgesia, Pain Medicine, Volume 16, Issue suppl_1, 1 October 2015, Pages S32–S36, https://doi.org/10.1111/pme.12914 [17]

3. PMID: 21412369- A comprehensive review of opioid-induced hyperalgesia. (pain physician) [16]

4. PMID: 29285750

5. PMID: 29594972

6. PMID: 26142224- Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

7. PMID: 22546966- Grégoire Blaudszun, Christopher Lysakowski, Nadia Elia, Martin R. Tramèr; Effect of Perioperative Systemic α2 Agonists on Postoperative Morphine Consumption and Pain Intensity: Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesthesiology 2012;116(6):1312-1322. doi: 10.1097/ALN.0b013e31825681cb. [20]

8. Opioid Switching: A systemic and critical review