Articles: neuropathic-pain.
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Transl Perioper Pain Med · Jan 2014
The Anti-Nociception Effect of Dezocine in a Rat Neuropathic Pain Model.
The treatment of neuropathic pain (NP) currently remains clinically challenging. In an attempt to identify novel targets of known opioids, we found that dezocine, a non-addictive opioid, inhibits norepinephrine and serotonin reuptake through their transporter proteins which open the potential for dezocine to manage NP. In the present study, the effect of dezocine on NP was observed in a rat model of chronic constriction injury (CCI). ⋯ PWL and PWT tests were performed at 11:00 AM starting from 1 day before CCI surgery and 1, 3, 7, 10 days after right sciatic nerve ligation in the presence or absence of daily intraperitoneal injection of dezocine. The results demonstrated that the CCI-induced thermal and mechanical pain hypersensitivity was attenuated by dezocine significantly and persistently without sign of tolerance, indicating that dezocine could be an alternative medication for the treatment of NP. Clinical trial to confirm such discovery is warranted.
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Journal of pain research · Jan 2014
The importance of catastrophizing for successful pharmacological treatment of peripheral neuropathic pain.
Catastrophizing may be a negative predictor of pain-related outcomes. We evaluated the impact of catastrophizing upon success of first-line pharmacotherapy in the management of neuropathic pain (NeP) due to peripheral polyneuropathy. ⋯ Catastrophizing exerts maladaptive effects on outcomes with pharmacotherapy in NeP patients. Detection of catastrophizing during clinical visits when pharmacological therapy is being considered can be a predictive factor for patient outcomes.
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Int J Clin Exp Patho · Jan 2014
Upregulation of neuregulin-1 reverses signs of neuropathic pain in rats.
Peripheral nerve injury can result in neuropathic pain, a chronic condition of unclear cause often poorly responsive to current treatments. One possibility is that nerve injury disrupts large A-fiber-mediated inhibition of C-fiber-evoked responses in spinal dorsal horn neurons, leading to central sensitization. A recent study provided a potential molecular mechanism; large dorsal root ganglion (DRG) neurons secrete neuregulin-1 (NRG1), which binds to erbB4 receptors on interneurons and promotes GABA release to inhibit C-fiber-evoked nociceptive transmission. Thus, reduced NRG1 expression following nerve injury could induce chronic pain by disinhibition. We examined if DRG expression of NRG1 is in fact reduced in a rat model of neuropathic pain and if exogenous NRG1 alleviates behavioral signs of this condition. ⋯ Our results are consistent with a model of neuropathic pain whereby peripheral nerve injury reduces NRG1-mediated inhibition of nociceptive signaling. Modulating NRG1 may have therapeutic potential for treating neuropathic pain.
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N-, T- and P/Q-type voltage-gated Ca(2+) channels are critical for regulating neurotransmitter release and cellular excitability and have been implicated in mediating pathological nociception. A-1264087 is a novel state-dependent blocker of N-, T- and P/Q-type channels. In the present studies, A-1264087 blocked (IC50 = 1.6 μM) rat dorsal root ganglia N-type Ca(2+) in a state-dependent fashion. ⋯ These effects by A-1264087 were not present in uninjured rats. A-1264087 moderately attenuated WDR neuron windup in both uninjured and SNL rats. In summary, these results indicate that A-1264087 selectively inhibited spinal nociceptive transmission in sensitized states through both peripheral and central mechanisms.
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Experimental neurology · Jan 2014
Kv2 dysfunction after peripheral axotomy enhances sensory neuron responsiveness to sustained input.
Peripheral nerve injuries caused by trauma are associated with increased sensory neuron excitability and debilitating chronic pain symptoms. Axotomy-induced alterations in the function of ion channels are thought to largely underlie the pathophysiology of these phenotypes. Here, we characterise the mRNA distribution of Kv2 family members in rat dorsal root ganglia (DRG) and describe a link between Kv2 function and modulation of sensory neuron excitability. ⋯ In accordance with a shortened AHP, ScTx treatment also reduced the refractory period and improved AP conduction to the cell soma during high frequency stimulation. These results suggest that Kv2 downregulation following traumatic nerve lesion facilitates greater fidelity of repetitive firing during prolonged input and thus normal Kv2 function is postulated to limit neuronal excitability. In summary, we have profiled Kv2 expression in sensory neurons and provide evidence for the contribution of Kv2 dysfunction in the generation of hyperexcitable phenotypes encountered in chronic pain states.