The
neuropeptide Substance P (SP), that has a high affinity for the neurokinin 1 (NK1) receptor, is involved in modulation of
pain transmission. Although SP is thought to have excitatory actions and promote nociception in the spinal cord, the
peptide induces
analgesia at the supraspinal level. The aim of this study was to evaluate the role of supraspinal SP and the NK1 receptor in inflammatory
pain induced by injection of
carrageenan in the hind paw of the rat. There are two nociceptive behavioral responses associated with this
pain state:
mechanical allodynia and heat
hyperalgesia. Because the NK1 receptor colocalizes with the MOP receptor in supraspinal sites involved in
pain modulation, we also decided to study the possible involvement of the
opioid system on SP-induced
analgesia. We found that treatment with SP, at doses of 3.5, 5 and 7 μg/5 μl/rat i.c.v., clearly showed inhibition of
allodynia and
hyperalgesia. Pretreatment with the selective NK1 antagonist
L-733,060 (10mg/kg i.p.) blocked the SP-induced
analgesia, suggesting the involvement of the NK1 receptor. This SP-induced
analgesia was significantly reduced by administration of the
opioid antagonist naloxone (3mg/kg s.c.). This reduction occurred when SP was administered either before or after the
carrageenan injection. These results suggest a significant antinociceptive role for SP and the NK1 receptor in inflammatory
pain at the supraspinal level, possibly through the release of endogenous
opioids.