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. 2024 Jan-Dec:20:17448069241260348.
doi: 10.1177/17448069241260348.

Morphine acts in vitro to directly prime nociceptors

Eugen V Khomula  1 , Jon D Levine  1   2
Affiliations

Morphine acts in vitro to directly prime nociceptors

Eugen V Khomula et al. Mol Pain. 2024 Jan-Dec.

Abstract

Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E2 (PGE2)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE2-induced nociceptor sensitization. In the present in vitro study we tested the hypothesis that a mu-opioid receptor (MOR) agonist opioid analgesic, morphine, can produce priming by its direct action on nociceptors. We report that treatment of nociceptors with morphine, in vitro, produces a leftward shift in the concentration dependence for PGE2-induced nociceptor sensitization. Our findings support the suggestion that opioids act directly on nociceptors to induce priming.

Keywords: Morphine; nociceptor; opioid-induced hyperalgesic priming; patch-clamp electrophysiology; prostaglandin E2; rheobase; sensitization.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Prior in vitro exposure of small-diameter DRG neurons to morphine produces persistent enhancement of PGE2-induced nociceptor sensitization. DRG neurons were exposed to morphine (20 µM) in their culturing media, for 1 h in a CO2 incubator, 24 h after establishing cultures. On the following 3 days after morphine exposure (48-96 h after establishing cultures), patch-clamp electrophysiology recordings were performed on small-diameter (≤30 µM) DRG neurons from control (opioid naïve) and morphine-treated cultures (depicted by the white and dark grey bars, correspondingly). Bars show average magnitudes of reduction in rheobase, relative to pre-administration baseline (measured before the first application of PGE2), and 5 min after application of 10 nM and then 100 nM. 10 nM PGE2 was applied first, and then, 10 min later, its concentration was increased to 100 nM (cumulative concentration dependence). Symbols show individual values. Only those neurons with a reduction in rheobase not less than 10%, for either the higher or lower concentration of PGE2, were considered for analysis. In morphine-treated neurons the effect of both concentrations of PGE2 was significantly greater than their effects in controls (two-way ANOVA: effect of treatment, ****p < .0001, F(1,43) = 20.2; Sidak's multiple comparisons test: t(43) = 3.3, ** adjusted p = .004 for 10 nM; t(43) = 3.1, ** adjusted p = .008 for 100 nM). Number of cells in control group: n = 20 for 10 nM and n = 15 for 100 nM; in primed group: n = 6 for both 10 nM and 100 nM. Number of rats (different culture preparations): six in control and three in primed group. Symbols with different color/shape combinations were used to show cells from different rats.
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References

    1. Ballantyne JC. Opioid therapy in chronic pain. Phys Med Rehabil Clin 2015; 26: 201–218. DOI: 10.1016/j.pmr.2014.12.001. - DOI - PubMed
    1. Bicket MC, Brat GA, Hutfless S, Wu CL, Nesbit SA, Alexander GC. Optimizing opioid prescribing and pain treatment for surgery: review and conceptual framework. Am J Health Syst Pharm 2019; 76: 1403–1412. DOI: 10.1093/ajhp/zxz146. - DOI - PubMed
    1. Cheung CW, Qiu Q, Choi SW, Moore B, Goucke R, Irwin M. Chronic opioid therapy for chronic non-cancer pain: a review and comparison of treatment guidelines. Pain Physician 2014; 17: 401–414. - PubMed
    1. Manchikanti L, Helm S, 2nd, Fellows B, Janata JW, Pampati V, Grider JS, Boswell MV. Opioid epidemic in the United States. Pain Physician 2012; 15: ES9–38. - PubMed
    1. Pisanu C, Franconi F, Gessa GL, Mameli S, Pisanu GM, Campesi I, Leggio L, Agabio R. Sex differences in the response to opioids for pain relief: a systematic review and meta-analysis. Pharmacol Res 2019; 148: 104447. DOI: 10.1016/j.phrs.2019.104447. - DOI - PubMed