Articles: hyperalgesia.
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The immune and sensory systems are known for their close proximity and interaction. Indeed, in a variety of pain states, a myriad of different immune cells are activated and recruited, playing a key role in neuronal sensitisation. During inflammatory pain it is thought that mast cells (MC) are one of the immune cell types involved in this process, but so far the evidence outlining their direct effect on neuronal cells remains unclear. ⋯ We also demonstrate that NGF treatment in vitro does not lead to an increased level of tumor necrosis factor-α in bone marrow-derived MC. Furthermore, our qRT-PCR data reveal that MC express negligible levels of NGF receptors, thereby explaining the lack of response to NGF. Together, our data suggest that MC do not play a direct role in peripheral sensitisation during inflammatory conditions.
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Experimental neurology · Jul 2017
Bilateral tactile hypersensitivity and neuroimmune responses after spared nerve injury in mice lacking vasoactive intestinal peptide.
Vasoactive intestinal peptide (VIP) is one of the neuropeptides showing the strongest up-regulation in the nociceptive pathway after peripheral nerve injury and has been proposed to support neuropathic pain. Nevertheless, the story may be more complicated considering the known suppressive effects of the peptide on the immune reactivity of microglial cells, which have been heavily implicated in the onset and maintenance of pain after nerve injury. We here used mice deficient in VIP and the model of spared nerve injury, characterized by persistent tactile hypersensitivity. ⋯ The latter was also observed at four weeks after spared nerve injury, a time at which bilateral tactile hypersensitivity persisted in VIP-deficient mice. These data suggest an action of VIP in neuropathic states that is more complicated than previously assumed. Future research is now needed for a deeper understanding of the relative contribution of receptors and fiber populations involved in the VIP-neuropathic pain link.
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The present study was designed to investigate the roles of P2X3 receptors in dorsal root ganglion (DRG) neurons in colonic hypersensitivity and the effects of alpha-lipoic acid (ALA) on P2X3 receptor activity and colonic hypersensitivity of diabetic rats. Streptozotocin (STZ) was used to induce diabetic model. Abdominal withdrawal reflex (AWR) responding to colorectal distention (CRD) was recorded as colonic sensitivity. ⋯ Importantly, ALA treatment attenuated colonic hypersensitivity in diabetic rats. Our data suggest that STZ injection increases expression and function of P2X3 receptors of colon-specific DRG neurons, thus contributing to colonic hypersensitivity in diabetic rats. Administration of ALA attenuates diabetic colonic hypersensitivity, which is most likely mediated by suppressing expression and function of P2X3 receptors in DRGs of diabetic rats.
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A bifunctional peptide containing an opioid and nociceptin receptor-binding pharmacophore, H-Dmt-D-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2 (KGNOP1), was tested for its analgesic properties when administered intrathecally in naïve and chronic constriction injury (CCI)-exposed rats with neuropathy-like symptoms. KGNOP1 significantly increased the acute pain threshold, as measured by the tail-flick test, and also increased the threshold of a painful reaction to mechanical and thermal stimuli in CCI-exposed rats. Both of the effects could be blocked by pre-administration of [Nphe1]-Nociceptin (1-13)-NH2 (NPhe) or naloxone, antagonists for nociceptin and opioid receptors, respectively. ⋯ Repeated daily intrathecal injections of KGNOP1 led to the development of analgesic tolerance, with the antiallodynic action being completely abolished on day 6. Nevertheless, the development of tolerance to the antihyperalgesic effect was delayed in comparison to morphine, which lost its efficacy as measured by the cold plate test after 3days of daily intrathecal administration, whereas KGNOP1 was efficient up to day 6. A single intrathecal injection of morphine to KGNOP1-tolerant rats did not raise the pain threshold in any of the behavioural tests; in contrast, a single intrathecal dose of KGNOP1 significantly suppressed allodynia and hyperalgesia in morphine-tolerant rats.
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Bmc Complem Altern M · Jun 2017
A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats.
The current therapy of neuropathic pain is inadequate and is limited by the extent of pain relief and the occurrence of dose dependant side effects. Insufficient control of pain with conventional medications prompts the use of complementary and alternative medicine therapies by patients with neuropathic pain. This study therefore investigated a standardized methanolic extract of Bacopa monnieri, a widely reputed nootropic plant, for prospective antinociceptive effect in the chronic constriction injury (CCI) model of neuropathic pain. ⋯ Our findings suggest that Bacopa monnieri can be used as adjuvant therapy for neuropathic pain conditions afflicted with allodynia and hyperalgesia.