Individual differences in the sensitivity of cold allodynia to phentolamine in neuropathic rats.

In neuropathic rats sensitive to phentolamine (alpha-adrenoreceptor antagonist, 2 mg/kg, i.p.), prazosin (alpha1-adrenoreceptor antagonist, 0.5 mg/kg, i.p.) significantly attenuated cold allodynia whereas yohimbine (alpha2-adrenoreceptor antagonist, 0.5 mg/kg, i.p.) had no significant effect. In neuropathic rats insensitive to phentolamine, yohimbine significantly exacerbated cold allodynia whereas prazosin had no significant effect. These results suggest that the individual differences in the sensitivity of cold allodynia to phentolamine may be due to the difference in the alpha-adrenoreceptor subtype predominantly involved in cold allodynia.

Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: mediation by spinal adrenergic and serotonergic receptors.

The present study was performed to examine the effects of electroacupuncture (EA) on cold allodynia and its mechanisms related to the spinal adrenergic and serotonergic systems in a rat model of neuropathic pain. For the neuropathic surgery, the right superior caudal trunk was resected at the level between S1 and S2 spinal nerves innervating the tail. Two weeks after the nerve injury, EA stimulation (2 or 100 Hz) was delivered to Zusanli (ST36) for 30 min. The behavioral signs of cold allodynia were evaluated by the tail immersion test [i.e., immersing the tail in cold water (4 degrees C) and measuring the latency to an abrupt tail movement] before and after the stimulation. And then, we examined the effects of intrathecal injection of prazosin (alpha1-adrenoceptor antagonist, 30 microg), yohimbine (alpha2-adrenoceptor antagonist, 30 microg), NAN-190 (5-HT1A antagonist, 15 microg), ketanserin (5-HT2A antagonist, 30 microg), and MDL-72222 (5-HT3 antagonist, 12 microg) on the action of EA stimulation. Although both 2 Hz and 100 Hz EA significantly relieved the cold allodynia signs, 2 Hz EA induced more robust effects than 100 Hz EA. In addition, intrathecal injection of yohimbine, NAN-190, and MDL-72222, but not prazosin and ketanserin, significantly blocked the relieving effects of 2 Hz EA on cold allodynia. These results suggest that low-frequency (2 Hz) EA is more suitable for the treatment of cold allodynia than high-frequency (100 Hz) EA, and spinal alpha2-adrenergic, 5-HT1A and 5-HT3, but not alpha1-adrenergic and 5-HT2A, receptors play important roles in mediating the relieving effects of 2 Hz EA on cold allodynia in neuropathic rats.

Effects of alpha1- and alpha2-adrenoreceptor antagonists on cold allodynia in a rat tail model of neuropathic pain.

Systemic administrations (0.1, 0.5, and 2 mg/kg) of alpha1-adrenoreceptor (AR) antagonist prazosin dose-dependently attenuated cold allodynia in a rat tail model of neuropathic pain, whereas alpha2-AR antagonist yohimbine exacerbated it. These results suggest that the functions of alpha1- and alpha2-AR in this model are excitatory and inhibitory, respectively, consistent with their general properties. It is also proposed that cold allodynia can be reversed by alpha1-AR antagonist and exacerbated by alpha2-AR antagonist.

Proteomic analysis of differential protein expression in neuropathic pain and electroacupuncture treatment models.

Acupuncture has long been used for pain relief. Although recent studies have shown that acupuncture can reduce neuropathic pain, the mechanism of this effect is not clear and little information is available regarding proteins that are involved in the development of neuropathic pain and the effects of acupuncture. We have developed an animal model for neuropathic pain using young adult male Sprague-Dawley rats. The model was confirmed by behavioral tests. Electroacupuncture (EA) treatment was applied to Zusanli (ST36) of neuropathic pain model to examine the analgesic effect of EA. The protein expression profile of the hypothalamus in both neuropathic pain and EA treatment models was analyzed using two-dimensional electrophoresis-based proteomics. We detected thirty-six proteins that were differentially expressed in the neuropathic pain model compared with normal rats and that restored to normal expression levels after EA treatment. Twenty-one of these proteins were identified in the MS-FiT database and are involved in a number of biological processes, including inflammation, enzyme metabolism and signal transduction. Potential applications of our results include the identification and characterization of signaling pathways involved in EA treatment and further exploration of the role of selected identified proteins in the animal model.

cDNA microarray analysis of the differential gene expression in the neuropathic pain and electroacupuncture treatment models.

Partial nerve injury is the main cause of neuropathic pain disorders in humans. Acupuncture has long been used to relieve pain. It is known to relieve pain by controlling the activities of the autonomic nervous system. Although the mechanism of neuropathic pain and analgesic effects of electroacupuncture (EA) have been studied in a rat model system, its detailed mechanism at the molecular level remains unclear. To identify genes that might serve as either markers or explain these distinct biological functions, a cDNA microarray analysis was used to compare the expression of 8,400 genes among three sample groups. Messenger RNAs that were pooled from the spinal nerves of 7 normal, 7 neuropathic pain, and 7 EA treatment rat models were compared. Sixty-eight genes were differentially expressed more than 2-fold in the neuropathic rat model when compared to the normal, and restored to the normal expression level after the EA treatment. These genes are involved in a number of biological processes, including the signal transduction, gene expression, and nociceptive pathways. Confirmation of the differential gene expression was performed by a dotblot analysis. Dot-blotting results showed that the opioid receptor sigma was among those genes. This indicates that opioid-signaling events are involved in neuropathic pain and the analgesic effects of EA. The potential application of these data include the identification and characterization of signaling pathways that are involved in the EA treatment, studies on the role of the opioid receptor in neuropathic pain, and further exploration on the role of selected identified genes in animal models.

Effects of electroacupuncture on the mechanical allodynia in the rat model of neuropathic pain.

The analgesic effects of acupuncture on the mechanical allodynia in the rat model of neuropathic pain have not yet been studied. The aim of the present study is: first, to determine if electroacupuncture (EA) or morphine attenuates the mechanical allodynia; and secondly, to examine if the EA effect may be mediated by endogenous opioids. To produce neuropathic pain, the right superior caudal trunk was resected between the S3 and S4 spinal nerves. Twenty-one days after the neuropathic surgery, low frequency EA stimulation (2 Hz, 0.3 ms, 0.07 mA) delivered to Houxi (S13) for 30 min relieved significantly the signs of mechanical allodynia. Intraperitoneal (i.p.) morphine (0.5 or 1.5 mg/kg) also relieved the signs of mechanical allodynia in a dose-dependent manner. In addition, the antiallodynic effect of Houxi EA was blocked by pretreatment with naloxone (2 mg/kg, i.p.). However, combined application of EA and morphine did not show an obvious synergistic effect. These results suggest that low frequency EA or morphine can relieve the mechanical allodynia signs and the EA effect can be mediated by endogenous opioid systems.