GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model.

Background: Peripheral hypersensitivities develop in the face and hindpaws of mice with nitroglycerin (NTG)-induced migraine. We evaluated whether diluted bee venom (DBV) injections at acupoints prevented these peripheral hypersensitivities and c-Fos expression in the trigeminal nucleus caudalis (TNC).

Methods: NTG (10 mg/kg, intraperitoneal, i.

The mTOR inhibitor rapamycin suppresses trigeminal neuropathic pain and p-MKK4/p-p38 mitogen-activated protein kinase-mediated microglial activation in the trigeminal nucleus caudalis of mice with infraorbital nerve injury.

Neuropathic pain caused by trigeminal nerve injury is a typical refractory orofacial chronic pain accompanied by the development of hyperalgesia and allodynia. We previously demonstrated that the mammalian target of rapamycin (mTOR) inhibitor rapamycin suppressed orofacial formalin injection-induced nociception; however, the underlying mechanism is unclear, and it is unknown whether it can reduce trigeminal neuropathic pain. In mice, left infraorbital nerve and partial nerve ligation (ION-pNL) was performed using a silk suture (8-0).

Different Involvement of ASIC and TRPA1 in Facial and Hindpaw Allodynia in Nitroglycerin-Induced Peripheral Hypersensitivities in Mice.

The pathophysiological mechanism underlying migraine-associated peripheral hypersensitivity remains unclear. Acid-sensing ion channels (ASICs) and transient receptor potential ankyrin 1 (TRPA1) are known to be causative pathogenic factors of mechanical and cold allodynia, respectively. Here, we sought to investigate their involvement in cold and mechanical allodynia of the face and hindpaws, respectively, in a mouse model of repetitive nitroglycerin (NTG)-induced migraine.

Dexmedetomidine Co-Administered with Lidocaine Decreases Nociceptive Responses and Trigeminal Fos Expression without Motor Dysfunction and Hypotension in a Murine Orofacial Formalin Model.

Administration of dexmedetomidine significantly induces sedation and anti-nociception in several nociceptive models, but clinical trials are restricted due to adverse side effects, including lethargy, hypotension, and bradycardia. Herein, we investigated whether intraperitoneal inoculation of dexmedetomidine reduced the orofacial nociceptive response and affected motor coordination and blood pressure and examined whether a lower dose of dexmedetomidine in combination with 0.5% lidocaine produced an antinociceptive effect without any adverse side events in a murine model.

Rapamycin reduces orofacial nociceptive responses and microglial p38 mitogen-activated protein kinase phosphorylation in trigeminal nucleus caudalis in mouse orofacial formalin model.

The mammalian target of rapamycin (mTOR) plays a role in various cellular phenomena, including autophagy, cell proliferation, and differentiation. Although recent studies have reported its involvement in nociceptive responses in several pain models, whether mTOR is involved in orofacial pain processing is currently unexplored. This study determined whether rapamycin, an mTOR inhibitor, reduces nociceptive responses and the number of Fos-immunoreactive (Fos-ir) cells in the trigeminal nucleus caudalis (TNC) in a mouse orofacial formalin model.

Analgesic Efficacy of α Adrenergic Receptor Agonists Depends on the Chronic State of Neuropathic Pain: Role of Regulator of G Protein Signaling 4.

The analgesic effect of alpha-2 adrenergic receptor (αAR) agonists, which relieve chronic neuropathic pain, is highly variable among individuals. Here, we used a mouse model of spared nerve injury (SNI) to show that treatment time after the establishment of neuropathic pain was important for the variability in the analgesic efficacy of αAR agonists, which was related to the activity of regulator of G-protein signaling protein 4 (RGS4). Intrathecal treatment with αAR agonists, clonidine (0.

Peripheral GABA receptor-mediated signaling facilitates persistent inflammatory hypersensitivity.

Unlike in the central nervous system (CNS), in the adult peripheral nervous system (PNS), activation of GABA receptors (GABAR) is excitatory because of the relatively high concentration of intracellular chloride in these neurons. Indeed, exogenous GABA and muscimol, a GABAR agonist, exacerbate acute inflammatory hypersensitivity in rodents. However, it remains unclear whether peripheral GABAR and the endogenous GABA play an important role in persistent inflammatory hypersensitivity.

Differential Development of Facial and Hind Paw Allodynia in a Nitroglycerin-Induced Mouse Model of Chronic Migraine: Role of Capsaicin Sensitive Primary Afferents.

Despite the relatively high prevalence of migraine or headache, the pathophysiological mechanisms triggering headache-associated peripheral hypersensitivities, are unknown. Since nitric oxide (NO) is well known as a causative factor in the pathogenesis of migraine or migraine-associated hypersensitivities, a mouse model has been established using systemic administration of the NO donor, nitroglycerin (NTG). Here we tried to investigate the time course development of facial or hindpaw hypersensitivity after repetitive NTG injection.

A critical role of spinal Shank2 proteins in NMDA-induced pain hypersensitivity.

Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD.

Clonidine, an alpha-2 adrenoceptor agonist relieves mechanical allodynia in oxaliplatin-induced neuropathic mice; potentiation by spinal p38 MAPK inhibition without motor dysfunction and hypotension.

Cancer chemotherapy with platinum-based antineoplastic agents including oxaliplatin frequently results in a debilitating and painful peripheral neuropathy. We evaluated the antinociceptive effects of the alpha-2 adrenoceptor agonist, clonidine on oxaliplatin-induced neuropathic pain. Specifically, we determined if (i) the intraperitoneal (i.

Repetitive Acupuncture Point Treatment with Diluted Bee Venom Relieves Mechanical Allodynia and Restores Intraepidermal Nerve Fiber Loss in Oxaliplatin-Induced Neuropathic Mice.

Unlabelled: The chemotherapeutic agent, oxaliplatin, produces a robust painful neuropathy that results in the loss of intraepidermal nerve fibers (IENFs). We have previously reported that an acupuncture point (acupoint) injection of diluted bee venom (DBV) produces a temporary antiallodynic effect in oxaliplatin-induced neuropathic mice. Herein we show a significant long-lasting antinociceptive effect of repetitive DBV acupoint treatment on oxaliplatin-induced mechanical allodynia and a significant reduction in the loss of IENFs.

Diluted bee venom injection reduces ipsilateral mechanical allodynia in oxaliplatin-induced neuropathic mice.

Oxaliplatin, which is used as one of anti-cancer drugs, commonly induces peripheral neuropathic pain. We have previously reported that an injection of diluted bee venom (DBV) produced a significant anti-nociceptive effects in several pain models of mice or rats. In this study, we evaluated time- and dose-dependent development of oxaliplatin-induced mechanical allodynia in bilateral hind paws of mice, and investigated the effect of DBV injection on this mechanical allodynia.