Change of vanilloid receptor 1 expression in dorsal root ganglion and spinal dorsal horn during inflammatory nociception induced by complete Freund’s adjuvant in rats

Abstract

The present study aimed to systematically observe the change of vanilloid receptor 1 (VR1) during inflammatory nociception induced by intraplantar injection of complete Freund's adjuvant (CFA) into the left hind paw in rats. Hot plate latency (HPL) was used to evaluate resulting thermal hyperalgesia and immunohistochemistry to observe VR1 expression in dorsal root ganglion and spinal cord dorsal horn. Results showed that HPL decreased from day 1 to day 28 after CFA injection, with shortest at day 14. VR1 expression correspondingly increased from day 1 to day 21 with peak at day 14, and returning to the control level at day 28. A shift of VRI expression from small to medium DRG neurons over the observation period was seen. These results suggest that VR1 could play an important role in the early stage, but not the late stage, of CFA inflammatory nociception.

The Orally Administered Selective TRPV1 Antagonist, JTS-653, Attenuates Chronic Pain Refractory to Non-steroidal Anti-inflammatory Drugs in Rats and Mice Including Post-herpetic Pain

“…This result implies that central sensitization would be involved in the mechanical hyperalgesia in the late phase of CFA-induced pain. The expression of TRPV1 in L5 DRG and in the superficial layers of the spinal dorsal horn were increased for 21 days after CFA injection (16), supporting the notion that CFAinduced mechanical hyperalgesia is related to central sensitization. Chronic inflammation and TRPV1 activation increased the neuropeptides and their receptors in the spinal nerve (28,29).…”

“…Otherwise, TRPV1 activation causes the release of neuropeptides in the spinal cord (12,13) leading to central sensitization (14). It has been reported that chronic inflammation and nerve injury affects the expression level (13,15,16) and distribution of TRPV1 (17). These observations suggest that TRPV1 plays a role in chronic pain.…”

TRPV1 Receptors in the CNS Play a Key Role in Broad-Spectrum Analgesia of TRPV1 Antagonists

“…Previous receptor expression studies have demonstrated that TRPV1 receptors are upregulated in both the periphery and the CNS during chronic inflammation (Carlton and Coggeshall, 2001;Ji et al, 2002;Luo et al, 2004). In addition, NGF, which has been shown to activate peripheral nociceptors, to affect gene expression at the cell body by retrograde signaling (Donnerer et al, 1992), and to be upregulated in peripheral tissue and DRG after inflammation and tissue injury (Woolf et al, 1994;Shu and Mendell, 1999;Amaya et al, 2004), can induce the upregulation of TRPV1 receptor expression and increase transport of TRPV1 to the peripheral nociceptor terminals (Ji et al, 2002).…”

Mechanisms of Prolonged Presynaptic Ca2+Signaling and Glutamate Release Induced by TRPV1 Activation in Rat Sensory Neurons

“…Although the question of which signals activate TRPV1 in vivo remains a matter of debate, numerous studies imply the importance of spinal cord TRPV1 for pain processing. Indeed, the receptor is significantly upregulated in the dorsal horn during chronic inflammation (Tohda et al, 2001;Luo et al, 2004), and intrathecal administration of either selective TRPV1 antagonists or small interfering RNAs that target TRPV1 produced strong analgesic effects in animal models of inflammatory, neuropathic, and visceral pain (Kelly and Chapman, 2002;Kanai et al, 2005;Christoph et al, 2006). Moreover, significant CNS penetration of orally administered TRPV1 antagonists was required to attenuate pain mediated by central sensitization (Cui et al, 2006).…”

“…At the peripheral terminals of primary nociceptors, TRPV1-mediated Ca 2ϩ influx triggers the release of neuropeptides, which contributes to the development of neurogenic inflammation (Caterina and Julius, 2001). TRPV1 is also found in the central processes of primary afferent neurons (Guo et al, 1999;Hwang et al, 2004), and its expression in the dorsal horn of the spinal cord is upregulated during chronic inflammation (Tohda et al, 2001;Luo et al, 2004). Notably, intrathecal administration of selective TRPV1 antagonists significantly reduces pain associated with inflammation and nerve injury (Kanai et al, 2005;Christoph et al, 2006;Cui et al, 2006).…”