Maturation of NK1 receptor involvement in the nociceptive response to formalin

Abstract

Administration of NK1 antagonists in adult animals attenuates the nociceptive response in the formalin test, indicating that the neurokinins and the NK1 receptor play a role in mediating this pain response. The number and distribution of NK1 receptors change dramatically during development, and the age at which they become involved in pain processing is not known. We examined the role of NK1 receptors in the formalin model in rats ranging in age between 3- and 21-days old. An NK1 antagonist, CP99,994, and its less active enantiomer CP100,263 were administered to the spinal cord (intrathecal), systemically (subcutaneous), or locally (intraplantar). Intrathecal administration of CP99,994, but not CP100,263, attenuated pain behaviors in the second phase of the formalin response in 14-day and 21-day old rats, but did not alter the pain response in 3-day or 10-day old rats. CP99,994 also reduced the expression of the c-fos protein in the superficial dorsal horn of 21-day old rats. Systemic and intraplantar injection of either CP99,994 or CP100,263 reduced the pain response to formalin in 3-day and 21-day old rats, suggesting a non-NK1 mediated mechanism of action. These results indicate that, within the spinal cord, NK1 receptors start to play a role in the pain response to formalin between 10 and 21 days. Moreover, analgesia induced by systemic or local injection of NK1 antagonists involves mechanisms other than, or in addition to, the NK1 receptor.

Effects of COX inhibition and LPS on formalin induced pain in the infant rat

“…Many pain processes that activate the immune system in the adult are immature in the infant. For example substance P and GABA are immune‐modulators [see for review: (Bost, ; Tuluc et al, ; Douglas and Leeman, ; Jin et al, ) but have delayed developmental trajectories in modulating pain (Fitzgerald and Gibson, ; King et al, , b; King and Barr, ; Baccei and Fitzgerald, ; Hathway et al, ; Zouikr et al, ). Thus injury that involves immune processes through either of these two neurotransmitters would have no consequence early in life.…”

Substance P (NK1) and somatostatin (sst2A) receptor immunoreactivity in NTS-projecting rat dorsal horn neurones activated by nociceptive afferent input

“…In situations such as tissue injury or inflammation, primary afferent inputs are believed to activate NK1 receptors on projection neurones relaying nociceptive signals to supraspinal nuclei concerned with pain perception and the control of spinal excitability through descending pathways to the spinal cord (reviewed by Todd, 2002). The importance of spinal NK1 receptors in these nociceptive responses has been shown in pharmacological studies applying specific antagonists to the dorsal horn (Ohkubo et al, 1990;Picard et al, 1993;King et al, 2000). Moreover, there is morphological evidence for the up-regulation of the NK1 receptor upon chronic noxious visceral stimulation (Ishigooka et al, 2001) and its internalisation on acute noxious, particularly thermal stimulation Abbadie et al, 1997;Allen et al, 1997).…”

Analgesia induced by local plantar injections of opiates in the formalin test in infant rats

“…Behavior was scan sampled (Martin & Bateson, 1993) every minute for 60 min. Behavior was rated on a five-point scale as adapted from Dubuisson & Dennis (1977) and modified as described previously (Barr, 1999;King, Cheng, Wang, & Barr, 2000). The behaviors recorded are given in Table 1.…”