IMR Press / JIN / Volume 23 / Issue 3 / DOI: 10.31083/j.jin2303064
Open Access Original Research
Blocking Pannexin 1 Channels Alleviates Peripheral Inflammatory Pain but not Paclitaxel-Induced Neuropathy
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1 Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil
2 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA
3 Department of Urology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA
4 Laboratory of Nerve Regeneration, University of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil
5 Institute of Biomedical Sciences, Department of Physiology, Federal University of Uberlandia (UFU), 38408-102 Uberlandia, MG, Brazil
*Correspondence: (Julia Borges Paes Lemes); (Carlos Amilcar Parada)
§Current address: Department of Anesthesiology, University of California San Diego, La Jolla, CA 92093, USA.
J. Integr. Neurosci. 2024, 23(3), 64;
Submitted: 14 October 2023 | Revised: 4 December 2023 | Accepted: 11 December 2023 | Published: 20 March 2024
(This article belongs to the Special Issue Advances in Migraine and Neuropathic Pain)
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Pannexin1 (Panx1) is a membrane channel expressed in different cells of the nervous system and is involved in several pathological conditions, including pain and inflammation. At the central nervous system, the role of Panx1 is already well-established. However, in the periphery, there is a lack of information regarding the participation of Panx1 in neuronal sensitization. The dorsal root ganglion (DRG) is a critical structure for pain processing and modulation. For this reason, understanding the molecular mechanism in the DRG associated with neuronal hypersensitivity has become highly relevant to discovering new possibilities for pain treatment. Here, we aimed to investigate the role of Panx1 in acute nociception and peripheral inflammatory and neuropathic pain by using two different approaches. Methods: Rats were treated with a selective Panx1 blocker peptide (10Panx) into L5-DRG, followed by ipsilateral intraplantar injection of carrageenan, formalin, or capsaicin. DRG neuronal cells were pre-treated with 10Panx and stimulated by capsaicin to evaluate calcium influx. Panx1 knockout mice (Panx1-KO) received carrageenan or capsaicin into the paw and paclitaxel intraperitoneally. The von Frey test was performed to measure the mechanical threshold of rats’ and mice’s paws before and after each treatment. Results: Pharmacological blockade of Panx1 in the DRG of rats resulted in a dose-dependent decrease of mechanical allodynia triggered by carrageenan, and nociception decreased in the second phase of formalin. Nociceptive behavior response induced by capsaicin was significantly lower in rats treated with Panx1 blockade into DRG. Neuronal cells with Panx1 blockage showed lower intracellular calcium response than untreated cells after capsaicin administration. Accordingly, Panx1-KO mice showed a robust reduction in mechanical allodynia after carrageenan and a lower nociceptive response to capsaicin. A single dose of paclitaxel promoted acute mechanical pain in wildtype (WT) but not in Panx1-KO mice. Four doses of chemotherapy promoted chronic mechanical allodynia in both genotypes, although Panx1-KO mice had significant ablation in the first eight days. Conclusion: Our findings suggest that Panx1 is critical for developing peripheral inflammatory pain and acute nociception involving transient receptor potential vanilloid subtype 1 (TRPV1) but is not essential for neuropathic pain chronicity.

inflammatory pain
#2017/19105-8/São Paulo Research Foundation (FAPESP)
#2019/15255-0/São Paulo Research Foundation (FAPESP)
001/Coordination for the Improvement of Higher Education Personnel (CAPES – Brazil)
Fig. 1.
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