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Divergent peripheral effects of pituitary adenylate cyclase-activating polypeptide-38 on nociception in rats and mice.
Pain. 2009 Jan; 141(1-2):143-50.PAIN

Abstract

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and its receptors have been shown in the spinal dorsal horn, on capsaicin-sensitive sensory neurons and inflammatory cells. The role of PACAP in central pain transmission is controversial, and no data are available on its function in peripheral nociception. Therefore, the aim of the present study was to analyze the effects of locally or systemically administered PACAP-38 on nocifensive behaviors, inflammatory/neuropathic hyperalgesia and afferent firing. Intraplantar PACAP-38 (0.2nmol) injection inhibited carrageenan-evoked inflammatory mechanical allodynia, mild heat injury-induced thermal hyperalgesia, as well as nocifensive behaviors in the early and late phases of the formalin test in rats. However, the above dose did not alter basal mechanical or heat thresholds. In mice, PACAP-38 (0.2nmol/kg s.c.) significantly diminished acetic acid-induced abdominal contractions, but exerted no effect on sciatic nerve ligation-induced neuropathic mechanical hyperalgesia. In contrast, local PACAP-38 injection markedly increased rotation-induced afferent firing in the inflamed rat knee joint clearly demonstrating a peripheral sensitization in this organ. These actions were blocked by VPAC1/VPAC2 receptor antagonist pretreatment, but were not altered by PAC1 receptor antagonism. This paper presents the first data for the peripheral actions of PACAP-38 on nociceptive transmission mediated by VPAC receptors. These effects seem to be divergent depending on the mechanisms of nociceptor activation and the targets of PACAP actions. In acute somatic and visceral inflammatory pain models, PACAP exerts anti-nociceptive, anti-hyperalgesic and anti-allodynic effects. It has no significant peripheral role in traumatic mononeuropathy, but induces mechanical sensitization of knee joint primary afferents.

Authors+Show Affiliations

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7624, Pécs, Szigeti u. 12., Hungary.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

19091468

Citation

Sándor, Katalin, et al. "Divergent Peripheral Effects of Pituitary Adenylate Cyclase-activating Polypeptide-38 On Nociception in Rats and Mice." Pain, vol. 141, no. 1-2, 2009, pp. 143-50.
Sándor K, Bölcskei K, McDougall JJ, et al. Divergent peripheral effects of pituitary adenylate cyclase-activating polypeptide-38 on nociception in rats and mice. Pain. 2009;141(1-2):143-50.
Sándor, K., Bölcskei, K., McDougall, J. J., Schuelert, N., Reglodi, D., Elekes, K., Petho, G., Pintér, E., Szolcsányi, J., & Helyes, Z. (2009). Divergent peripheral effects of pituitary adenylate cyclase-activating polypeptide-38 on nociception in rats and mice. Pain, 141(1-2), 143-50. https://doi.org/10.1016/j.pain.2008.10.028
Sándor K, et al. Divergent Peripheral Effects of Pituitary Adenylate Cyclase-activating Polypeptide-38 On Nociception in Rats and Mice. Pain. 2009;141(1-2):143-50. PubMed PMID: 19091468.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Divergent peripheral effects of pituitary adenylate cyclase-activating polypeptide-38 on nociception in rats and mice. AU - Sándor,Katalin, AU - Bölcskei,Kata, AU - McDougall,Jason J, AU - Schuelert,Niklas, AU - Reglodi,Dóra, AU - Elekes,Krisztián, AU - Petho,Gábor, AU - Pintér,Erika, AU - Szolcsányi,János, AU - Helyes,Zsuzsanna, Y1 - 2008/12/16/ PY - 2008/02/19/received PY - 2008/10/11/revised PY - 2008/10/30/accepted PY - 2008/12/19/entrez PY - 2008/12/19/pubmed PY - 2009/4/9/medline SP - 143 EP - 50 JF - Pain JO - Pain VL - 141 IS - 1-2 N2 - Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and its receptors have been shown in the spinal dorsal horn, on capsaicin-sensitive sensory neurons and inflammatory cells. The role of PACAP in central pain transmission is controversial, and no data are available on its function in peripheral nociception. Therefore, the aim of the present study was to analyze the effects of locally or systemically administered PACAP-38 on nocifensive behaviors, inflammatory/neuropathic hyperalgesia and afferent firing. Intraplantar PACAP-38 (0.2nmol) injection inhibited carrageenan-evoked inflammatory mechanical allodynia, mild heat injury-induced thermal hyperalgesia, as well as nocifensive behaviors in the early and late phases of the formalin test in rats. However, the above dose did not alter basal mechanical or heat thresholds. In mice, PACAP-38 (0.2nmol/kg s.c.) significantly diminished acetic acid-induced abdominal contractions, but exerted no effect on sciatic nerve ligation-induced neuropathic mechanical hyperalgesia. In contrast, local PACAP-38 injection markedly increased rotation-induced afferent firing in the inflamed rat knee joint clearly demonstrating a peripheral sensitization in this organ. These actions were blocked by VPAC1/VPAC2 receptor antagonist pretreatment, but were not altered by PAC1 receptor antagonism. This paper presents the first data for the peripheral actions of PACAP-38 on nociceptive transmission mediated by VPAC receptors. These effects seem to be divergent depending on the mechanisms of nociceptor activation and the targets of PACAP actions. In acute somatic and visceral inflammatory pain models, PACAP exerts anti-nociceptive, anti-hyperalgesic and anti-allodynic effects. It has no significant peripheral role in traumatic mononeuropathy, but induces mechanical sensitization of knee joint primary afferents. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/19091468/Divergent_peripheral_effects_of_pituitary_adenylate_cyclase_activating_polypeptide_38_on_nociception_in_rats_and_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(08)00675-1 DB - PRIME DP - Unbound Medicine ER -