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NO/cGMP production is important for the endogenous peripheral control of hyperalgesia during inflammation.
Nitric Oxide. 2013 Jan 15; 28:8-13.NO

Abstract

Various studies have demonstrated the role of the nitric oxide (NO)/cGMP pathway in pain processing. Our group has also shown that this system participates in opioid-induced antinociception during peripheral inflammation. We have previously observed that inflammation mobilizes an endogenous opioidergic system to control hyperalgesia. Here, we investigated whether the NO/cGMP pathway underlies peripheral endogenous nociception control during inflammation. In this study, a pharmacological approach was used in conjunction with the rat paw pressure test to assess the effects of intraplantar NO synthase inhibitor NG-Nitro-l-arginine (NOArg), guanylyl cyclase inhibitor methylene blue (MB), phosphodiesterase-5 inhibitor zaprinast (ZP), or NO precursor l-arginine injection on carrageenan-induced hyperalgesia, which mimics an inflammatory process, or by prostaglandin E(2) (PGE(2)), which directly sensitizes nociceptors. Intraplantar carrageenan (62.5, 125, 250 or 500μg) or PGE(2) (0.1, 0.5 or 2μg) administration produced hyperalgesia, which manifested as a reduction in the rat nociceptive threshold to mechanical stimuli. NOArg (25, 50 or 100μg/paw) and MB (125, 250 or 500μg/paw) induced significant and dose-dependent reductions in the nociceptive threshold of carrageenan-induced (125μg/paw) hyperalgesia, but not PGE(2)-induced (0.5μg/paw) hyperalgesia. This was a local effect because it did not produce any modifications in the contralateral paw. Both Zaprinast (100, 200 or 400μg/paw) and l-arginine (100, 200 or 400μg/paw) significantly counteracted carrageenan-induced hyperalgesia (250μg/paw), yielding an increase in the nociceptive threshold compared with the control. Zaprinast (200μg/paw) or l-arginine (400μg/paw) did not produce an antinociceptive effect in the contralateral paw, indicating local action. In addition, at the same dose that was able to modify carrageenan-induced hyperalgesia, neither zaprinast nor l-arginine modified PGE(2) (2μg) injection-induced hyperalgesia of the rat paw. Taken together, these results indicate that the l-arginine/NO/cGMP pathway functions as an endogenous modulator of peripheral inflammatory hyperalgesia.

Authors+Show Affiliations

Department of Pharmacology, Institute of Biological Sciences, ICB-UFMG, Av. Antônio Carlos 6627, Pampulha, CEP 31.270-100 Belo Horizonte, MG, Brazil. danielapereiraalves@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22995857

Citation

Alves, Daniela P., et al. "NO/cGMP Production Is Important for the Endogenous Peripheral Control of Hyperalgesia During Inflammation." Nitric Oxide : Biology and Chemistry, vol. 28, 2013, pp. 8-13.
Alves DP, da Motta PG, Romero TR, et al. NO/cGMP production is important for the endogenous peripheral control of hyperalgesia during inflammation. Nitric Oxide. 2013;28:8-13.
Alves, D. P., da Motta, P. G., Romero, T. R., Klein, A., & Duarte, I. D. (2013). NO/cGMP production is important for the endogenous peripheral control of hyperalgesia during inflammation. Nitric Oxide : Biology and Chemistry, 28, 8-13. https://doi.org/10.1016/j.niox.2012.09.001
Alves DP, et al. NO/cGMP Production Is Important for the Endogenous Peripheral Control of Hyperalgesia During Inflammation. Nitric Oxide. 2013 Jan 15;28:8-13. PubMed PMID: 22995857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NO/cGMP production is important for the endogenous peripheral control of hyperalgesia during inflammation. AU - Alves,Daniela P, AU - da Motta,Patrícia G, AU - Romero,Thiago R L, AU - Klein,André, AU - Duarte,Igor D G, Y1 - 2012/09/17/ PY - 2011/12/29/received PY - 2012/08/29/revised PY - 2012/09/09/accepted PY - 2012/9/22/entrez PY - 2012/9/22/pubmed PY - 2014/8/12/medline SP - 8 EP - 13 JF - Nitric oxide : biology and chemistry JO - Nitric Oxide VL - 28 N2 - Various studies have demonstrated the role of the nitric oxide (NO)/cGMP pathway in pain processing. Our group has also shown that this system participates in opioid-induced antinociception during peripheral inflammation. We have previously observed that inflammation mobilizes an endogenous opioidergic system to control hyperalgesia. Here, we investigated whether the NO/cGMP pathway underlies peripheral endogenous nociception control during inflammation. In this study, a pharmacological approach was used in conjunction with the rat paw pressure test to assess the effects of intraplantar NO synthase inhibitor NG-Nitro-l-arginine (NOArg), guanylyl cyclase inhibitor methylene blue (MB), phosphodiesterase-5 inhibitor zaprinast (ZP), or NO precursor l-arginine injection on carrageenan-induced hyperalgesia, which mimics an inflammatory process, or by prostaglandin E(2) (PGE(2)), which directly sensitizes nociceptors. Intraplantar carrageenan (62.5, 125, 250 or 500μg) or PGE(2) (0.1, 0.5 or 2μg) administration produced hyperalgesia, which manifested as a reduction in the rat nociceptive threshold to mechanical stimuli. NOArg (25, 50 or 100μg/paw) and MB (125, 250 or 500μg/paw) induced significant and dose-dependent reductions in the nociceptive threshold of carrageenan-induced (125μg/paw) hyperalgesia, but not PGE(2)-induced (0.5μg/paw) hyperalgesia. This was a local effect because it did not produce any modifications in the contralateral paw. Both Zaprinast (100, 200 or 400μg/paw) and l-arginine (100, 200 or 400μg/paw) significantly counteracted carrageenan-induced hyperalgesia (250μg/paw), yielding an increase in the nociceptive threshold compared with the control. Zaprinast (200μg/paw) or l-arginine (400μg/paw) did not produce an antinociceptive effect in the contralateral paw, indicating local action. In addition, at the same dose that was able to modify carrageenan-induced hyperalgesia, neither zaprinast nor l-arginine modified PGE(2) (2μg) injection-induced hyperalgesia of the rat paw. Taken together, these results indicate that the l-arginine/NO/cGMP pathway functions as an endogenous modulator of peripheral inflammatory hyperalgesia. SN - 1089-8611 UR - https://www.unboundmedicine.com/medline/citation/22995857/NO/cGMP_production_is_important_for_the_endogenous_peripheral_control_of_hyperalgesia_during_inflammation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1089-8603(12)00385-0 DB - PRIME DP - Unbound Medicine ER -