Articles: neuralgia.
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Peripheral nerve stimulation (PNS) is a neuromodulation technique in which electrical current is applied to the peripheral nerves to ameliorate chronic pain through preferential activation of myelinated fibres, inducing long-term depression of synaptic efficacy. External noninvasive peripheral nerve stimulation (EN-PNS) is a novel and simple form of PNS that involves stimulation via an external nerve-mapping probe that is placed on the skin and connected to a power source. ⋯ In this first prospective report on the use of EN-PNS in neuropathic pain, this technology provided significant clinical benefit for some patients. Controlled studies are required to confirm our results and the place of EN-PNS in future neuromodulation treatment algorithms. Given the refractory nature of these conditions, these results are encouraging.
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The Journal of physiology · Jul 2015
Impairment of adenylyl cyclase-mediated glutamatergic synaptic plasticity in the periaqueductal grey in a rat model of neuropathic pain.
Long-lasting neuropathic pain has been attributed to elevated neuronal plasticity changes in spinal, peripheral and cortical levels. Here, we found that reduced neuronal plasticity in the ventrolateral periaqueductal grey (vlPAG), a midbrain region important for initiating descending pain inhibition, may also contribute to neuropathic pain. Forskolin- and isoproterenol (isoprenaline)-elicited EPSC potentiation was impaired in the vlPAG of a rat model of neuropathic pain induced by spinal nerve injury. Down-regulation of adenylyl cyclase-cAMP- PKA signalling, due to impaired adenylyl cyclase, but not phosphodiesterase, in glutamatergic terminals may contribute to the hypofunction of excitatory synaptic plasticity in the vlPAG of neuropathic rats and the subsequent descending pain inhibition, ultimately leading to long-lasting neuropathic pain. Our results suggest that drugs that activate adenylyl cyclase in the vlPAG have the potential for relieving neuropathic pain. ⋯ Neuropathic pain has been attributed to nerve injury-induced elevation of peripheral neuronal discharges and spinal excitatory synaptic plasticity while little is known about the contribution of neuroplasticity changes in the brainstem. Here, we examined synaptic plasticity changes in the ventrolateral (vl) periaqueductal grey (PAG), a crucial midbrain region for initiating descending pain inhibition, in spinal nerve ligation (SNL)-induced neuropathic rats. In vlPAG slices of sham-operated rats, forskolin, an adenylyl cyclase (AC) activator, produced long-lasting enhancement of EPSCs. This is a presynaptic effect since forskolin decreased the paired-pulse ratio and failure rate of EPSCs, and increased the frequency, but not the amplitude, of miniature EPSCs. Forskolin-induced EPSC potentiation was mimicked by a β-adrenergic agonist (isoproterenol (isoprenaline)), and prevented by an AC inhibitor (SQ 22536) and a cAMP-dependent protein kinase (PKA) inhibitor (H89), but not by a phosphodiesterase (PDE) inhibitor (Ro 20-1724) or an A1 -adenosine antagonist (DPCPX). Both forskolin- and isoproterenol-induced EPSC potentiation was impaired in PAG slices of SNL rats. The SNL group had lower AC, but not PDE, activity in PAG synaptosomes than the sham group. Conversely, IPSCs in vlPAG slices were not different between SNL and sham groups. Intra-vlPAG microinjection of forskolin alleviated SNL-induced mechanical allodynia in rats. These results suggest that SNL leads to inadequate descending pain inhibition resulting from impaired glutamatergic synaptic plasticity mediated by the AC-cAMP-PKA signalling cascade, possibly due to AC down-regulation in the PAG, leading to long-term neuropathic pain.
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Deep brain stimulation (DBS) is a commonly performed procedure and has been used for the treatment of chronic pain since the early 1970s. A review of the literature was performed utilizing the PubMed database evaluating the use of DBS in the treatment of various pain syndromes. Literature over the last 30 years was included with a focus on those articles in the last 10 years dealing with pain conditions with the highest success as well as the targets utilized for treatment. ⋯ Cephaligias have promising results, with cluster headaches carrying the best success rates. DBS plays a role in the treatment of chronic pain conditions. Although considered investigational in the USA, it carries promising success rates in a recalcitrant patient population.
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Molecular pharmacology · Jul 2015
CB1 Knockout Mice Unveil Sustained CB2-Mediated Antiallodynic Effects of the Mixed CB1/CB2 Agonist CP55,940 in a Mouse Model of Paclitaxel-Induced Neuropathic Pain.
Cannabinoids suppress neuropathic pain through activation of cannabinoid CB1 and/or CB2 receptors; however, unwanted CB1-mediated cannabimimetic effects limit clinical use. We asked whether CP55,940 [(-)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexanol], a potent cannabinoid that binds with similar affinity to CB1 and CB2 in vitro, produces functionally separable CB1- and CB2-mediated pharmacological effects in vivo. We evaluated antiallodynic effects, possible tolerance, and cannabimimetic effects (e.g., hypothermia, catalepsy, CB1-dependent withdrawal signs) after systemic CP55,940 treatment in a mouse model of toxic neuropathy produced by a chemotherapeutic agent, paclitaxel. ⋯ High-dose CP55,940 did not produce hypothermia or rimonabant-precipitated withdrawal in CB1KO mice. Our results using the mixed CB1/CB2 agonist CP55,940 document that CB1 and CB2 receptor activations produce mechanistically distinct suppression of neuropathic pain. Our study highlights the therapeutic potential of targeting cannabinoid CB2 receptors to bypass unwanted central effects associated with CB1 receptor activation.
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Chronic pain due to spinal dural arteriovenous fistulae (SDAVF) during follow-up is a serious issue because it can affect patients' quality of life. The severity of posttreatment chronic leg pain in patients with SDAVF is unclear. ⋯ Most of our SDAVF patients reported moderate to severe chronic leg pain characterized by spontaneous pain and paresthesia/dysesthesia. Spinal cord atrophy on magnetic resonance imaging scans was a characteristic in patients with chronic pain.