sb-366791 and Facial-Pain

Topics: Acrolein; Anilides; Animals; Calcium; Calcium Signaling; Capsaicin; Cinnamates; Disease Models, Animal; Facial Pain; Glutamic Acid; HEK293 Cells; Humans; Inhibitory Concentration 50; Male; Neuropeptides; Nociception; Patch-Clamp Techniques; Rats; Sensory System Agents; Transfection; Trigeminal Ganglion; TRPA1 Cation Channel; TRPV Cation Channels

Thermal and mechanical hypersensitivity in the injured region is a common complication. Although it is well known clinically that thermal and mechanical sensitivity of the oral mucosa is different from that of the skin, the mechanisms underlying injured pain of the oral mucosa remain poorly understood. The transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) in primary afferent neurons are known to contribute to pathological pain. Therefore, we investigated whether TRPV1 and/or TRPA1 contribute to thermal and mechanical hypersensitivity following oral mucosa or whisker pad skin incision. Strong heat and mechanical and cold hypersensitivity was caused in the buccal mucosa and whisker pad skin following incisions. On day 3 after the incisions, the number of TRPV1-immunoreactive (IR) and TRPA1-IR trigeminal ganglion (TG) neurons innervating the buccal mucosa and whisker pad skin was significantly increased, and the number of TRPV1/TRPA1-IR TG neurons innervating whisker pad skin, but not the buccal mucosa, was significantly increased. Administration of the TRPV1 antagonist, SB366791, to the incised site produced a significant suppression of heat hyperalgesia in both the buccal mucosa and whisker pad skin, as well as mechanical allodynia in the whisker pad skin. Administration of the TRPA1 antagonist, HC-030031, to the incised site suppressed mechanical allodynia and cold hyperalgesia in both the buccal mucosa and whisker pad skin, as well as heat hyperalgesia in the whisker pad skin. These findings indicate that altered expressions of TRPV1 and TRPA1 in TG neurons are involved in thermal and mechanical hypersensitivity following the buccal mucosa and whisker pad skin incision. Moreover, diverse changes in the number of TRPV1 and TRPA1 coexpressed TG neurons in whisker pad skin-incised rats may contribute to the intracellular interactions of TRPV1 and TRPA1 associated with whisker pad skin incision, whereas TRPV1 and TRPA1 expression in individual TG neurons is involved in buccal mucosa-incised pain.

Topics: Acetanilides; Anilides; Animals; Cinnamates; Cold Temperature; Electromyography; Facial Pain; Hot Temperature; Hyperalgesia; Male; Mouth Mucosa; Neurons; Pain; Purines; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion; TRPA1 Cation Channel; TRPC Cation Channels; TRPV Cation Channels; Vibrissae

Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head-withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection.

Topics: Acetanilides; Anilides; Animals; Behavior, Animal; Capsaicin; Cinnamates; Cold Temperature; Electromyography; Face; Facial Pain; Hot Temperature; Hyperalgesia; Injections, Intradermal; Male; Neural Conduction; Neurons; Physical Stimulation; Purines; Rats; Rats, Sprague-Dawley; Reflex; Sensory System Agents; Synaptic Transmission; Trigeminal Ganglion; TRPA1 Cation Channel; TRPC Cation Channels; TRPV Cation Channels

Chronic pain often develops in the orofacial region after inferior alveolar nerve (IAN) injury. In animal models IAN injury often causes severe neuropathic pain-like behavior in the IAN-innervated region as well as the adjacent region that includes the whisker pad skin. However, the basis for the spreading of pain to adjacent facial areas after IAN injury is still unknown. In this study we determined if the transient receptor potential vanilloid 1 (TRPV1) was associated with altered nocifensive behavior evoked by stimulation of the whisker pad skin following IAN transection. Grooming behavior after capsaicin injection into the whisker pad region was significantly increased after IAN transection and the increase in the behavior was reversed by systemic administration of a TRPV1 antagonist. The number of phosphorylated extracellular signal-regulated kinase immunoreactive (IR) neurons in trigeminal spinal subnucleus caudalis and upper cervical spinal cord following capsaicin injection into the whisker pad region was significantly greater in IAN-transected rats than sham-operated rats. The number of TRPV1-IR trigeminal ganglion (TG) neurons innervating the whisker pad skin was also increased significantly after IAN transection. The present findings suggest that an increase in TRPV1 expression in TG neurons innervating the whisker pad skin after IAN transection may underlie the spreading of pain to the adjacent whisker pad skin.

Topics: Anilides; Animals; Antigens, Nuclear; Behavior, Animal; Capsaicin; Cell Count; Cinnamates; Electric Stimulation; Extracellular Signal-Regulated MAP Kinases; Facial Pain; Grooming; Immunohistochemistry; Male; Mandibular Nerve; Nerve Tissue Proteins; Phosphorylation; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion; TRPV Cation Channels; Vibrissae