Pain
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Comparative Study
Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain.
Proinflammatory cytokines are mediators of inflammatory and neuropathic pain. Here, we investigated pain-related behavior in rats after intraneural injection of different doses of rat recombinant interleukin-1beta (rrIL-1beta) and tumor necrosis factor-alpha (rrTNF) into the sciatic nerve. Doses ranged between 0.25 and 2500pg/ml for rrIL-1beta and 0.25-250pg/ml for rrTNF. ⋯ However, this did not reflect the extent of behavioral changes. In summary, we found a bell-shaped dose-response curve for the algesic effects of rrIL-1beta and rrTNF, peaking at doses equivalent to those of endogenous cytokines released locally after nerve injury. The absence of corresponding morphological changes in nerves supports the concept of a functional effect of the cytokines at these doses.
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Comparative Study
Use of a novel thermal operant behavioral assay for characterization of orofacial pain sensitivity.
Orofacial pain has been well-characterized clinically, but evaluation of orofacial pain in animals has not kept pace. The objective of this study was to describe behavioral responses to facial thermal stimulation and inflammation with/without an analgesic using a novel operant paradigm. Animals were trained to voluntarily place their face against a stimulus thermode (37.7-57.2 degrees C) providing access to positive reinforcement. ⋯ These outcomes were significantly affected in the direction of increased nociception following inflammation, and these indices of hyperalgesia were reversed with morphine administration. These data reflect an orofacial pain behavior profile that was based on an animal's responses in an operant escape paradigm. This technique allows evaluation of nociceptive processing and modulation throughout the neuraxis.
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Comparative Study
Effects of gabapentin on spontaneous discharges and subthreshold membrane potential oscillation of type A neurons in injured DRG.
Ectopic spontaneous discharges play a critical role for both initiation and maintenance of the neuropathic pain state. Gabapentin (GBP) has been shown to be effective in animal models of neuropathic pain as well as in chronic pain patients. To investigate the peripheral mechanisms of GBP, the effects of GBP on spontaneous discharges and subthreshold membrane potential oscillation (SMPO) of chronically compressed dorsal root ganglion (DRG) were examined electrophysiolocally in vitro. ⋯ Furthermore, we found that the SMPO of injured DRG cells can be selectively abolished by GBP without interrupting spike propagation. The results suggest that the inhibitory effect of GBP on SMPO might be one of the membrane mechanisms of action of GBP. This may partially explain the antinociceptive action of GBP by directly suppression nociceptive afferent input to the spinal cord.
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Comparative Study Clinical Trial
Dorsal root entry zone (DREZ) localization using direct spinal cord stimulation can improve results of the DREZ thermocoagulation procedure for intractable pain relief.
The dorsal root entry zone (DREZ) thermocoagulation for intractable pain after brachial plexus avulsion was performed in 21 patients. Good results in pain relief (relief of more than 75% of preoperative pain) were achieved in 62% of patients, whereby fair results (relief of 25-75% of preoperative pain) in 38% of patients. There was no patient with poor result (relief of less than 25% of preoperative pain). ⋯ Comparing with the Group 1 consisting of nine patients (n=9), where the localization of DREZ by evoked potentials was not performed, significantly better effect of pain relief was recorded (P<0.05, odds ratio 10). There was no statistically significant difference (P>0.7) in complication rate in Group 1 and Group 2. Described electrophysiological technique is very helpful in identifying of DREZ and, in combination with microsurgical technique, can create DREZ thermocoagulation more effective.
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Comparative Study
Enhancement of NMDA receptor phosphorylation of the spinal dorsal horn and nucleus gracilis neurons in neuropathic rats.
NR1 is an essential component of functional NMDA receptors and can be activated by phosphorylation. It is suggested that phosphorylation of NR1 (pNR1) contributes to central sensitization after intradermal capsaicin injection. The present study investigates whether increases of spinal pNR1 are correlated to central sensitization and thus pain behaviors in neuropathic pain. ⋯ A protein kinase A inhibitor, H89, moderately reversed mechanical allodynia in 7 day neuropathic rats. Many pNR1-immunoreactive neurons were identified as projection neurons by retrograde tracer. The data suggest that PKA mediated NMDA receptor phosphorylation plays an important role in spinal nerve ligation induced neuropathic pain.