This study examined the differential mechanisms of
mechanical allodynia and
thermal hyperalgesia after injection of
interleukin (IL) 1β into the orofacial area of male Sprague-Dawley rats. The subcutaneous administration of IL-1β produced both
mechanical allodynia and
thermal hyperalgesia. Although a pretreatment with
iodoresiniferatoxin (IRTX), a transient receptor potential vanilloid 1 (TRPV1) antagonist, did not affect IL-1β-induced
mechanical allodynia, it significantly abolished IL-1β-induced
thermal hyperalgesia. On the other hand, a pretreatment with D-AP5, an
N-methyl-d-aspartate (
NMDA) receptor antagonist, and
NBQX, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
acid (
AMPA) receptor antagonist, blocked IL-1β-induced
mechanical allodynia. Pretreatment with
H89, a
protein kinase A (
PKA) inhibitor, blocked IL-1β-induced
mechanical allodynia but not
thermal hyperalgesia. In contrast, pretreatment with
chelerythrine, a
protein kinase C (PKC) inhibitor, inhibited IL-1β-induced
thermal hyperalgesia.
Subcutaneous injections of 2%
lidocaine, a
local anesthetic agent, blocked IL-1β-induced
thermal hyperalgesia but not IL-1β-induced
mechanical allodynia. In the
resiniferatoxin (RTX)-pretreated rats, a
subcutaneous injection of IL-1β did not produce
thermal hyperalgesia due to the depletion of TRPV1 in the primary afferent fibers. Double immunofluorescence revealed the colocalization of PKA with
neurofilament 200 (NF200) and of PKC with the
calcitonin gene-related peptide (CGRP) in the trigeminal ganglion. Furthermore,
NMDA receptor 1 (NR1) and TRPV1 predominantly colocalize with PKA and PKC, respectively, in the trigeminal ganglion. These results suggest that IL-1β-induced
mechanical allodynia is mediated by sensitized peripheral
NMDA/
AMPA receptors through PKA-mediated signaling in the large-diameter primary afferent nerve fibers, whereas IL-1β-induced
thermal hyperalgesia is mediated by sensitized peripheral TRPV1 receptors through PKC-mediated signaling in the small-diameter primary afferent nerve fibers.