Involvement of PACAP receptor in primary afferent fibre‐evoked responses of ventral roots in the neonatal rat spinal cord

Abstract

1 The role of PACAP receptor in nociceptive transmission was investigated in vitro using maxadilan, a PACAP receptor selective agonist and max.d.4, a PACAP receptor selective antagonist. 2 Potentials, from a ventral root (L3 ± L5) of an isolated spinal cord preparation or a spinal cord ± saphenous nerve ± skin preparation from 0 ± 3-day-old rats, were recorded extracellularly.

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

“…The fact, that PACAP shows increased expression in the superficial layer of the spinal dorsal horn and in capsaicin-sensitive primary sensory neurons, suggested that it has a role in nociception [33,34,39,[61][62][63]. However, the results obtained from the early in vivo studies proved to be contradictory [41]. Intrathecally administered PACAP-38 showed analgesic effect in the early phase, subsequently followed by a long-lasting algesia in the formalin test [48].…”

“…In several other models centrally applied PACAP showed marked pro-nociceptive effects: it decreased thermal stimulation-evoked paw withdrawal latencies and potentiated nociceptive transmission to the dorsal horn [37]. It facilitated spinal nociceptive flexor reflexes [41,60] and induced hyperalgesia [35]. We provided evidence that PACAP-38 exerts an interesting divergent effect on pain-signaling.…”

cAMP activation by PACAP/VIP stimulates IL‐6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells

“…IL-6 produced by osteoblasts/stromal cells has been demonstrated as a key factor for excessive bone resorption in physiological conditions such as postmenopausal osteoporosis (Suda et al, 1991;Pfeilschifter et al, 2002;, hyperparathyroidism (Grey et al, 1999) and Paget's disease (Roodman, 2001). Considering the fact that PACAP mainly functions as neurotransmitter and PACAP positive nerve fibers and receptors were found in bone tissue (Strange-Vognsen et al, 1997;Togari et al, 1997;Ransjo et al, 2000;Lundberg et al, 2001;Sakashita et al, 2001;Uddman et al, 2002), we examined the rapid responses of proinflammatory cytokines mediated by PACAP/VIP in MC3T3 cells. Cells were transfected with control RNAi (Luciferase) or VPAC2-R RNAi (VPAC2-R #2) to examine VPAC2-R dependency, and then either not treated or treated with PACAP or VIP (10 À7 M) for 3 h to stimulate cytokines release into medium (Fig.…”

“…Interestingly, nerve fibers containing PACAP were observed at moderate density in both the trigeminal nucleus caudalis and in the Rexed's laiminae I and II of the dorsal horns at the C1 and C2 levels in human (Uddman et al, 2002). PACAP receptor is dominantly distributed in the neonatal rat spinal cord (Sakashita et al, 2001) and PACAP immunoreactivity nerve fibers were found in the porcine epiphyseal cartilage canals innervating blood vessels (Strange-Vognsen et al, 1997). In addition, receptors for PACAP/VIP are expressed in bone tissue.…”

Spinal astrocyte-neuron lactate shuttle contributes to the PACAP/PAC1 receptor-induced nociceptive behaviors

“…Pituitary adenylate cyclase-activating polypeptide (PACAP) was originally isolated from ovine hypothalamic extracts based on its ability to stimulate adenylate cyclase in rat anterior pituitary cell cultures ( Miyata et al, 1989; Miyata et al, 1990 ). In normal state, PACAP specific receptor, PAC1 receptor, is particularly abundant in central nervous system (CNS) including spinal dorsal horn ( Dickinson et al, 1999;Jongsma et al, 2000;Sakashita et al, 2001;Vaudry et al, 2009; Yokai et al, 2016 ), where PACAP-immunoreactive fibers are also considerably localized ( Moller et al, 1993; Dun et al, 1996a; Dun et al, 1996b; Narita et al, 1996 ), and PACAP mRNA/immunoreactivity in rat dorsal root ganglia is markedly upregulated in peripheral nerve injury or inflammation ( Zhang et al, 1995; Zhang et al, 1998; Jongsma et al, 2003; Mabuchi et al, 2004 ). These observations coupled with other lines of evidence propose that PACAP/PAC1 receptor system could play an important role in the modulation of spinal nociceptive transmission.…”