Delta opioid receptor-mediated analgesia is not altered in preprotachykinin A knockout mice.
We have shown that delta opioid receptor (DOPR)-mediated analgesia was enhanced in the complete Freund's adjuvant (CFA) model of inflammation. This effect is thought to originate from translocation of DOPR in the plasma membrane of dorsal root ganglia and spinal cord neurons. Among the putative mechanisms involved in the regulation of DOPR trafficking, an interaction with substance P (SP) in large dense-core vesicles has been described as an essential event for the externalization of DOPR. As we have previously observed that membrane DOPRs were upregulated in small- and medium-sized neurons under inflammatory pain conditions (whereas SP is mainly expressed by small dorsal root ganglia neurons), we raised the hypothesis that an SP-independent mechanism mediates DOPR trafficking and functional emergence in the CFA model. Therefore, we investigated the role of SP in DOPR-mediated analgesia by using preprotachykinin A (precursor of SP) knockout mice (PPTA(-/-) ) in the CFA model of inflammation. First, we confirmed that PPTA(-/-) mice are not expressing SP and have a similar level of CFA-induced inflammation as wildtype mice. Then, using the thermal plantar test, we found that an intrathecal injection of deltorphin II induced DOPR-mediated antihyperalgesia, which was not modified by the absence of SP (similar efficacy and potency in wildtype and PPTA(-/-) mice). We also observed similar analgesia of intrathecal deltorphin II for PPTA(-/-) and wildtype mice in the hot-water immersion tail-flick test. Consequently, our results suggest that SP is not essential for membrane insertion and for the functional emergence of DOPR.
Département de physiologie et biophysique, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
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Dubois
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Gendron
D000698:Analgesia; D000818:Animals; D001522:Behavior, Animal; D005620:Freund's Adjuvant / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009474:Neurons / Q000378:metabolism; D009842:Oligopeptides / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D010147:Pain Measurement; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics* / Q000378:metabolism*
D009842:Oligopeptides; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D015320:Tachykinins; C044206:preprotachykinin; C060209:deltorphin II, Ala(2)-; D013373:Substance P; D005620:Freund's Adjuvant