Articles: neuropathic-pain.
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Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.e. ⋯ In contrast, the response threshold to acute nociceptive stimulation was not affected by any of the compounds tested. Most of the amino acids in the heptapeptide structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapeptide and its N-terminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.
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ATP/ADP-evoked spinal astrocyte activation plays a vital role in the development of neuropathic pain. We aim to investigate the role of mammalian target of rapamycin (mTOR) pathway on the spinal astrocyte activation in the neuropathic pain development in rats. ⋯ Our data demonstrated that ADP enhanced neuropathic pain in CCI rats, which was inhibited by rapamycin. This study indicates that targeting mTOR pathway could serve as a novel therapeutic strategy in neuropathic pain management.
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This study was designed to determine whether acute or chronic venlafaxine administration was effective in alleviating symptoms of neuropathic pain in a rat model of neuropathic pain, and whether the effect of venlafaxine involved manipulation of α2-adrenoceptors,by determining the effect of yohimbine, a α2-adrenoceptor antagonist on its actions. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted in stimulus-evoked thermal hyperalgesia, tactile mechanical and cold allodynia. Acute venlafaxine injections (20 and 40 mg/kg i.p.) on the 7th, 14th and 21st postoperative days could not reduce tactile and cold hypersensitivity significantly compared to CCI group. ⋯ Also the effect of venlafaxine on heat hyperalgesia was reversed by pretreatment with yohimbine at all-time intervals. These results indicate that venlafaxine, when administered immediately after nerve injury, and for a sufficient period of time, can prevent the development and expression of neuropathic pain. Also we conclude that α2-adrenoceptors participate in the antinociceptive effects of venlafaxine.
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Neuroscience letters · Sep 2014
The expression of calcium/calmodulin-dependent protein kinase II in the dorsal horns of rats with type 1 and type 2 diabetes.
The activation of calcium/calmodulin-dependent protein kinase II (CaMKII) has been proposed as a key factor in chronic pain development. This study therefore aimed to investigate the expression of CaMKII in the dorsal horn in a rat model of early phase diabetes mellitus (DM) types 1 and 2. Sprague-Dawley rats were used. ⋯ No difference in IB4 expression was observed between the groups. These results suggest a potential role for CaMKII in diabetic neuropathy development. Inhibition of CaMKII signaling pathways should be further explored as a potential treatment target in painful diabetic neuropathy.
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J Pain Palliat Care Pharmacother · Sep 2014
The pharmacokinetics, efficacy, safety, and ease of use of a novel portable metered-dose cannabis inhaler in patients with chronic neuropathic pain: a phase 1a study.
Chronic neuropathic pain is often refractory to standard pharmacological treatments. Although growing evidence supports the use of inhaled cannabis for neuropathic pain, the lack of standard inhaled dosing plays a major obstacle in cannabis becoming a "main stream" pharmacological treatment for neuropathic pain. The objective of this study was to explore the pharmacokinetics, safety, tolerability, efficacy, and ease of use of a novel portable thermal-metered-dose inhaler (tMDI) for cannabis in a cohort of eight patients suffering from chronic neuropathic pain and on a stable analgesic regimen including medicinal cannabis. ⋯ A significant 45% reduction in pain intensity was noted 20 minutes post inhalation (P = .001), turning back to baseline within 90 minutes. Tolerable, lightheadedness, lasting 15-30 minutes and requiring no intervention, was the only reported adverse event. This trial suggests the potential use of the Syqe Inhaler device as a smokeless delivery system of medicinal cannabis, producing a Δ(9)-THC pharmacokinetic profile with low interindividual variation of Cmax, achieving pharmaceutical standards for inhaled drugs.