Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models.

Abstract

There is accumulating evidence that substance P released from peripheral sensory neurons participates in inflammatory and neuropathic pain. In this study it was investigated the ability of substance P to induce orofacial nociception and thermal and mechanical hyperalgesia, as well as the role of NK1 receptors on models of orofacial inflammatory and neuropathic pain. Substance P injected into the upper lip at 1, 10 and 100 μg/50 μL failed to induce nociceptive behavior. Also, substance P (0.1-10 μg/50 μL) injected into the upper lip did not evoke orofacial cold hyperalgesia and when injected at 1 μg/50 μL did not induce mechanical hyperalgesia. However, substance P at this latter dose induced orofacial heat hyperalgesia, which was reduced by the pre-treatment of rats with a non-peptide NK1 receptor antagonist (SR140333B, 3mg/kg). Systemic treatment with SR140333B (3 mg/kg) also reduced carrageenan-induced heat hyperalgesia, but did not exert any influence on carrageenan-induced cold hyperalgesia. Blockade of NK1 receptors with SR140333B also reduced by about 50% both phases of the formalin response evaluated in the orofacial region. Moreover, heat, but not cold or mechanical, hyperalgesia induced by constriction of the infraorbital nerve, a model of trigeminal neuropathic pain, was abolished by pretreatment with SR140333B. Considering that substance P was peripherally injected (i.e. upper lip) and the NK1 antagonist used lacks the ability to cross the blood-brain-barrier, our results demonstrate that the peripheral SP/NK1 system participates in the heat hyperalgesia associated with inflammation or nerve injury and in the persistent pain evoked by formalin in the orofacial region.

• Authors: Fernanda C Teodoro, Marcos F Tronco Júnior, Aleksander R Zampronio, Alessandra C Martini, Giles A Rae, Juliana G Chichorro
• Journal: Neuropeptides (Neuropeptides) Vol. 47 Issue 3 Pg. 199-206 (Jun 2013) ISSN: 1532-2785 [Electronic] Netherlands
• PMID: 23177733 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Neurokinin-1 Receptor Antagonists
• Receptors, Neurokinin-1
• SR140333B
• Tropanes
• Substance P

Topics

• Animals
• Behavior, Animal (drug effects, physiology)
• Cold Temperature
• Constriction, Pathologic (pathology)
• Facial Pain (chemically induced, physiopathology, psychology)
• Grooming (drug effects)
• Hot Temperature
• Hyperalgesia (physiopathology, psychology)
• Inflammation (chemically induced, physiopathology)
• Injections
• Lip
• Male
• Neuralgia (chemically induced, physiopathology, psychology)
• Neurokinin-1 Receptor Antagonists (pharmacology)
• Pain Measurement
• Physical Stimulation
• Rats
• Rats, Wistar
• Receptors, Neurokinin-1 (drug effects)
• Substance P (administration & dosage, pharmacology)
• Tropanes (pharmacology)