Aberrant TRPV1 Expression in Heat Hyperalgesia Associated with Trigeminal Neuropathic Pain

Abstract

Trigeminal neuropathic pain is a facial pain syndrome associated with trigeminal nerve injury. However, the mechanism of trigeminal neuropathic pain is poorly understood. This study aimed to determine the role of transient receptor potential vanilloid 1 (TRPV1) in heat hyperalgesia in a trigeminal neuropathic pain model. We evaluated nociceptive responses to mechanical and heat stimuli using a partial infraorbital nerve ligation (pIONL) model. Withdrawal responses to mechanical and heat stimuli to vibrissal pads (VP) were assessed using von Frey filaments and a thermal stimulator equipped with a heat probe, respectively. Changes in withdrawal responses were measured after subcutaneous injection of the TRP channel antagonist capsazepine. In addition, the expression of TRPV1 in the trigeminal ganglia was examined. Mechanical allodynia and heat hyperalgesia were observed in VP by pIONL. Capsazepine suppressed heat hyperalgesia but not mechanical allodynia. The number of TRPV1-positive neurons in the trigeminal ganglia was significantly increased in the large-diameter-cell group. These results suggest that TRPV1 plays an important role in the heat hyperalgesia observed in the pIONL model.

Abnormal trigeminal sensory processing in obese mice

“…A similar shift has been observed in rats following neuropathic injury. 50 This may have implications for nociceptive transmission since medium/large diameter neurons have faster conduction velocity. Future studies with retrograde neuronal labelling and electrophysiological assessment of neuronal excitation and firing will investigate the functional changes in specific subpopulations of trigeminal neurons.…”

Peripheral afferents and spinal inhibitory system in dynamic and static mechanical allodynia

“…Therefore, in mice, we may expect no significant contribution of TRPV1-expressing nociceptors to static mechanical allodynia unless they acquire such mechanosensitivity, or other mechanosensitive afferents start expressing TRPV1 in pathological conditions. Such abnormal function/expression of TRPV1 after nerve injury [12; 32; 54; 55] would confound the afferent type identification based on afferents’ reactivity to TRPV1 agonists/antagonists. Interestingly, ‘neonatal ablation’ of TRPV1-expressing nociceptors in rats did not prevent static mechanical allodynia after nerve injury in adulthood [48].…”

Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects

“…TRPV1 receptors are highly expressed in small-diameter primary sensory neurons in dorsal root ganglia (DRG) and trigeminal ganglia (TG) (Caterina et al, 1997;Tominaga, 2010;Urano et al, 2012) and are reported to be involved in inflammation (Amaya et al, 2003), cancer (Asai et al, 2005;Shinoda et al, 2008) and neuropathic pain (Hudson et al, 2001;Rashid et al, 2003;Fukuoka et al, 2002). In orofacial pain, a role for TRPV1 receptors has been described after tooth pulp inflammation (Chidiac et al, 2002;Tarsa et al, 2010), temporomandibular disorders (TMD) (Ro et al, 2009), oral cancer (Nagamine et al, 2006) and pain induced by nerve injury (Kim et al, 2008).…”

“…In orofacial pain, a role for TRPV1 receptors has been described after tooth pulp inflammation (Chidiac et al, 2002;Tarsa et al, 2010), temporomandibular disorders (TMD) (Ro et al, 2009), oral cancer (Nagamine et al, 2006) and pain induced by nerve injury (Kim et al, 2008). More specifically in the infraorbital nerve constriction model, it has been demonstrated that TRPV1 receptors are up-regulated after the injury and that pharmacological blockade or selective ablation of trigeminal ganglia cells expressing TRPV1 results impaired the development of facial heat hyperalgesia (Urano et al, 2012;Cruz et al, 2014). Additionally, it has been shown that the pharmacological desensitization of receptors is a fundamental mechanism for modulating the activity of the sensory system (St Pierre et al, 2009).…”

“…Therefore, the results presented herein suggest that the inhibitory effects of B vitamins, especially B1 vitamins, on heat hyperalgesia may involve desensitization of the TRPV1 receptors. A limitation of our study was the performance of calcium imaging experiments in a heterologous system, although the role of TRPV1 receptors in heat hyperalgesia after infraorbital nerve injury in rats has been well established (Urano et al, 2012;Cruz et al, 2014). However, further studies should be addressed in order to explore the importance of this mechanism for the analgesic effects of B vitamins on heat hyperalgesia associated with trigeminal neuropathic pain.…”