Background & Aims
Monotherapy can only be beneficial for the management of chronic pain, such as neuropathic pain when a single molecule can sustain its therapeutic response without producing adverse effects throughout prolonged treatment. Although gabapentinoids remain as the most commonly prescribed drugs to treat neuropathic pain, new research suggests that this drug is widely misused and can lead to undesirable effects alone or in combination with other drugs. One of the most serious risk factors is the combination with opioids. It is suggested that the combination of an opioid and a cannabinoid to treat neuropathic pain at lower doses without sacrificing the beneficial effects of the medication or the negative effects to prevent antinociceptive tolerance during long-term treatments in preclinical models can be an alternative to existing treatments.
The aim was to determine the maximal antiallodynic and anti-hyperalgesic effects of the combination.
Methods
Male Wistar rats weighing 150–180 g were used. The antinociceptive effects of an acute administration of 16 combinations of tramadol (1.0, 3.16, 5.62, 10 mg/kg) and PEA (0.0316, 0.10, 0.316, 1.0 mg/kg) 12 days after the ligation of the sciatic nerve were evaluated.
When the most effective combination was found, it was compared to the dose that had the greatest antinociceptive effect of each individual drug to determine whether repeated dosing (8 days) created side effects or lost its antinociceptive effect.
Results
The antinociceptive efficacy of TRA10 + PEA0.0316 mg/kg was comparable to that of the maximum doses of each drug (TRA 31.62 mg/kg and PEA 3.16 mg). The combination of TRA10 + PEA 0.0316 retained its antinociceptive efficacy after 8 days of treatment without changes in motor coordination or constipation.
Conclusions
Repeated administrations of TRA10 + PEA0.0316 mg/g in a neuropathic pain model generate antinociceptive effects equivalent to those produced by the highest doses of PEA or TRA alone, but without the induction of side effects.
References
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Mersfelder, T. L., & Nichols, W. H. (2016). Gabapentin: Abuse, Dependence, and Withdrawal. In Annals of Pharmacotherapy (Vol. 50, Issue 3, pp. 229–233). SAGE Publications Inc. https://doi.org/10.1177/1060028015620800
Morrison, E. E., Sandilands, E. A., & Webb, D. J. (2017). Gabapentin and pregabalin: Do the benefits outweigh the harms? Journal of the Royal College of Physicians of Edinburgh, 47(4), 310–313. https://doi.org/10.4997/JRCPE.2017.402