naloxone and Trigeminal-Neuralgia

Eslicarbazepine acetate (ESL) is a novel dibenzazepine antiepileptic, that has demonstrated efficacy against trigeminal pain, both in preclinical and clinical studies. However, ESL's mechanism of antinociceptive action remains uncertain. Here, we aimed to examine the contribution of adrenergic/cholinergic/opioid receptors to the antinociceptive effects of ESL in a trigeminal pain model, as these neurotransmitter systems are known to have an important role in the modulation of trigeminal nociception.. ESL's effects in the orofacial formalin test were examined following peroral and local peripheral administration (subcutaneous, into the perinasal region). The involvement of adrenergic/cholinergic/opioid receptors was evaluated by intraperitoneally pretreating mice with an appropriate antagonist immediately after peroral application of ESL. We used antagonists of α. ESL dose-dependently reduced formalin-induced nociceptive behavior after systemic and local peripheral application. Systemic administration of yohimbine, propranolol, metoprolol, atropine and naloxone inhibited ESL's antinociceptive effects in a dose-related manner. Prazosin and mecamylamine did not produce inhibitory effects. Local application of yohimbine, atropine and naloxone into the perinasal area also produced a dose-related inhibition of ESL's efficacy, whereas metoprolol failed to inhibit the local antinociceptive effects of ESL.. This study suggests that ESL's efficacy against trigeminal nociception is mediated by peripheral (and possibly central) α

Topics: Adrenergic Antagonists; Analgesics; Animals; Atropine; Cholinergic Antagonists; Dibenzazepines; Formaldehyde; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Receptors, Adrenergic; Receptors, Cholinergic; Receptors, Opioid; Trigeminal Neuralgia; Yohimbine

To investigate the effects of morphine on mechanical allodynia following compression of the trigeminal ganglion in the rat.. Experiments were carried out on male Sprague-Dawley rats weighing between 250 and 260 g. For compression, a 4% agar solution (8 microL) was injected into the trigeminal ganglion. In the control group, rats were sham operated without agar injections. The authors evaluated the effects of intraperitoneal or intracisternal administration of morphine on mechanical allodynia evoked by air-puff stimulation of the vibrissa pad area 14 days following compression of the trigeminal ganglion.. Mechanical allodynia was established within 3 days and lasted beyond postoperative day 24. Intraperitoneal administration of morphine (2 or 5 mg/kg) significantly blocked mechanical allodynia ipsilateral to the compression of the trigeminal ganglion. Intraperitoneal administration of morphine also inhibited mechanical allodynia on the contralateral side. Moreover, intracisternal administration of morphine (5 microg) strongly suppressed both ipsilateral and contralateral mechanical allodynia. The antiallodynic effects of morphine were blocked by pretreatment with naloxone, an opioid receptor antagonist.. These results suggest that the application of a high dose of morphine may be of great benefit in treating trigeminal neuralgia-like nociception.

Topics: Animals; Cisterna Magna; Facial Pain; Injections; Injections, Intraperitoneal; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Nerve Compression Syndromes; Physical Stimulation; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion; Trigeminal Neuralgia; Vibrissae

Trigeminal neuropathic pain represents a real challenge to therapy because commonly used drugs are devoid of real beneficial effect or patients frequently become intolerant or refractory to some of these compounds. In a rat model of trigeminal neuropathic pain, which shares numerous similarities with human trigeminal neuralgia and trigeminal neuropathic pain, we used a genomic herpes simplex virus-derived vector (HSVLatEnk) to examine the possible effect of a local overproduction of proenkephalin A (PA) targeted to the trigeminal primary sensory neurons. Unilateral peripheral inoculation of recombinant vectors on the vibrissal pad territory resulted in an about ninefold increase in proenkephalin A mRNA levels in trigeminal ganglion ipsilateral to the infected side. Transgene-derived met-enkephalin accumulated in numerous nerve cell bodies of trigeminal ganglion and was transported through the sensory nerve fibers located in the infraorbital nerve. Bilateral mechanical hyperresponsiveness, which developed 2 weeks after chronic constrictive injury of the left infraorbital nerve, was significantly attenuated in animals overproducing PA in the trigeminal ganglion ipsilateral to the lesioned infraorbital nerve. This antiallodynic effect was reversed by both the opioid receptor antagonist naloxone and the peripherally acting antagonist naloxone methiodide. Our data demonstrate that the local overproduction of PA-derived peptides in trigeminal ganglion sensory neurons evoked a potent antiallodynic effect through the stimulation of mainly peripherally located opioid receptors and suggest that targeted delivery of endogenous opioids may be of interest for the treatment of some severe forms of neuropathic pain.

Topics: Animals; Disease Models, Animal; Enkephalins; Genetic Therapy; Male; Naloxone; Narcotic Antagonists; Neurons; Pain Threshold; Protein Precursors; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; RNA, Messenger; Simplexvirus; Transcriptional Activation; Trigeminal Ganglion; Trigeminal Neuralgia

We report on the response of medically refractory neuropathic trigeminal pain in three patients to intravenous administration of a combination of the kappa-partial agonist opioid nalbuphine and the opioid antagonist naloxone. Each of the three patients had developed a painful peripheral neuropathy as a complication of chemical or mechanical injury to the trigeminal nerve. Each patient had been tried on a number of analgesics, including mu-opioids, and had not gained relief or was not able to tolerate side effects of the medications. Pain intensity was measured for 3 h following drug administration using a 10 cm visual analog scale. All three patients reported marked decrease in pain following administration of the nalbuphine and naloxone combination. These findings suggest a novel approach to the management for neuropathic pain.

Topics: Adult; Analgesics, Opioid; Drug Combinations; Female; Humans; Male; Nalbuphine; Naloxone; Narcotic Antagonists; Pain Measurement; Time Factors; Trigeminal Neuralgia

The influence of naloxone (a narcotic antagonist), bicuculline (a GABA antagonist), phentolamine (an alpha-blocking agent), propranolol (a beta-adrenergic blocking agent), haloperidol (a dopaminergic blocking agent), methysergide (a serotonergic blocking agent) and atropine (a muscarinic blocking agent), on the antinociceptive effects induced by carbamazepine, baclofen, pentazocine and morphine, were investigated with a new antinociception test, using the trigeminal pain induced by application of bradykinin onto the tooth pulp of the rat. The antinociceptive effect of carbamazepine was significantly inhibited by bicuculline, phentolamine, propranolol and haloperidol but not by naloxone, methysergide and atropine. The effect of baclofen was significantly reduced by naloxone, bicuculline, propranolol and atropine but not by phentolamine, haloperidol and methysergide. The antinociceptive actions of pentazocine and morphine on trigeminal pain were significantly reduced by naloxone and phentolamine, and by naloxone alone, respectively. These results suggest the involvement of different neurotransmitters in the antinociceptive effects of the four analgesic drugs on trigeminal pain induced by bradykinin.

Topics: Analgesics; Animals; Atropine; Baclofen; Bicuculline; Bradykinin; Carbamazepine; Haloperidol; Male; Methysergide; Morphine; Naloxone; Neurotransmitter Agents; Pentazocine; Rats; Rats, Inbred Strains; Sympatholytics; Trigeminal Neuralgia; Trigeminal Nucleus, Spinal