Articles: hyperalgesia.
-
We evaluated the role of a mechanically-gated ion channel, Piezo2, in mechanical stimulation-induced enhancement of hyperalgesia produced by the pronociceptive vasoactive mediator endothelin-1, an innocuous mechanical stimulus-induced enhancement of hyperalgesia that is vascular endothelial cell dependent. We also evaluated its role in a preclinical model of a vascular endothelial cell dependent painful peripheral neuropathy. ⋯ These results support the hypothesis that Piezo2 is a mechano-transducer in the endothelial cell where it contributes to stimulus-dependent hyperalgesia, and a model of chemotherapy-induced painful peripheral neuropathy.
-
Neuroscience letters · Oct 2015
Tetrodotoxin suppresses thermal hyperalgesia and mechanical allodynia in a rat full thickness thermal injury pain model.
Burn injuries have been identified as the primary cause of injury in 5% of U. S. military personnel evacuated from Operations Iraqi Freedom and Enduring Freedom. Severe burn-associated pain is typically treated with opioids such as fentanyl, morphine, and methadone. ⋯ Thermal hyperalgesia and mechanical allodynia were assessed 60 and 120 min post injection on each day of TTX treatment. TTX significantly reduced thermal hyperalgesia at all days tested and had a less robust, but statistically significant suppressive effect on mechanical allodynia. These results suggest that systemic TTX may be an effective, rapidly acting analgesic for battlefield burn injuries and has the potential for replacing or reducing the need for opioid analgesics.
-
Despite the clinical relevance of nocebo effects, few studies have addressed their underlying neural mechanisms in clinically-relevant pain models. We aimed to address the contribution of nocebo effects and their underlying neural circuitry to central pain amplification in visceral pain, as it may develop over repeated painful experiences due to negative pain-related expectations. Healthy volunteers received verbal suggestions of pain sensitization (nocebo group, N=28) or neutral instructions (control group, N=16). fMRI was used to investigate changes in neural responses during cued pain anticipation and painful rectal distensions delivered in successive fMRI sessions. ⋯ A subsequent psycho-physiological interaction analysis of the pain phase showed increased functional connectivity between the anterior insula, which was set-up as seed region based on group results, and midcingulate cortex as a function of negative expectations. These findings support that negative pain-related expectations can play a crucial role in pain amplification of visceral pain, which is mediated, at least in part, by a neural up-regulation of pain-associated areas and their connectivity. These findings may have implications for the pathophysiology and treatment of chronic abdominal pain.
-
Painful diabetic neuropathy is a common complication of diabetes mellitus, which often makes the patients suffer from severe hyperalgesia and allodynia. Thus far, the treatment of painful diabetic neuropathy remains unsatisfactory. Metformin, which is the first-line drug for type-2 diabetes, has been proved to attenuate hyperexcitability in sensory neurons linked to chemotherapy-induced neuropathic pain, highlighting its potential in alleviating pain related with painful diabetic neuropathy. ⋯ Further studies showed that metformin could activate AMPK and increase the AMPK target genes in sciatic nerves in diabetic rats. In conclusion, metformin is able to attenuate diabetes-induced hyperalgesia and allodynia, which might be associated its anti-oxidative effect through AMPK pathway. Metformin might be used as an effective drug, especially with fewer side effects, for abnormal sensation in painful diabetic neuropathy.
-
Brain research bulletin · Oct 2015
The spinal antinociceptive mechanism determined by systemic administration of BD1047 in zymosan-induced hyperalgesia in rats.
Although sigma-1 receptor (Sig-1R) antagonists have a potential antinociceptive effect in inflammatory diseases, the precise mechanism is not fully understood. The present study was aimed to elucidate the role of spinal neurons and microglia in the anti-nociceptive mechanism of BD1047 (a prototypical Sig-1R antagonist) using an inflammatory pain model based on intraplantar injection of zymosan. Oral pretreatment with BD1047 dose-dependently reduced zymosan-induced thermal and mechanical hyperalgesia as well as spinal neuronal activation including increased immunoreactivity of Fos, protein kinase C (PKC) and 'PKC-dependent phosphorylation of the NMDA receptor subunit 1' (pNR1). ⋯ In the spinal cord section, Sig-1R immunoreactivity was exclusively distributed in both spinal dorsal horn neurons and central endings of unmyelinated primary afferent fibers but not in glia. Intrathecal injection of BD1047 alleviated zymosan-induced hyperalgesia up to the level of oral administration. Taken together, our data imply that antinociceptive effect induced by oral treatment with BD1047 may be mediated, at least in part, by the inhibition of neuronal and microglial activation in the spinal cord triggered by inflammatory conditions.