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.