Biomedical subjects

Chengshui Zhao

Publications and source records attributed to Chengshui Zhao.

6 recordsLinked to original sources

PubMed2005

Enhanced thermal avoidance in mice lacking the ATP receptor P2X3.

P2X3 is an ATP-gated cation channel subtype expressed by a subpopulation of primary sensory neurons. In vivo spinal cord recordings in mice lacking P2X3 (P2X3-/-) have suggested that this protein may be important for the coding of peripheral warm stimuli. To explore this possibility more thoroughly, we examined behavioral and electrophysiological responses to thermal stimuli in P2X3-/- mice. As previously reported, recording from the spinal cord dorsal horn of anesthetized P2X3-/- mice revealed a blunted response of wide dynamic range neurons to hind paw heating. When placed in a thermal gradient, however, P2X3-/- mice exhibited an unexpectedly enhanced avoidance of both hot and cold temperatures, relative to controls. In the tail immersion test, mutant mice exhibited shorter withdrawal latencies at temperatures above and below thermoneutrality. Consistent with these changes, P2X3-/- mice exhibited enhanced induction of spinal cord c-FOS following hind paw heating to 45 degrees C. Thus, gain- and loss-of-function thermosensory phenotypes coexist in P2X3-/- mice. No changes in thermal preference were observed in wild-type mice injected subcutaneously with the P2X3 antagonist, A317491 or intrathecally with the P2X3 and P2X1 antagonist TNP-ATP. The reason for this apparent discrepancy is unclear, but we cannot exclude the possibility that compensatory events contribute, at least in part, to the P2X3-/- phenotype. Regardless, this study illustrates the utility of thermal preference assays as part of a comprehensive approach to the analysis of mouse thermosensation.

Analysis of Variance↗

PubMed2004

Tart cherry anthocyanins suppress inflammation-induced pain behavior in rat.

The use of complementary and alternative medicine (CAM) has increased in the United States and more patients are seeking CAM therapies for control of pain. The present investigation tested the efficacy of orally administered anthocyanins extracted from tart cherries on inflammation-induced pain behavior in rats. Paw withdrawal latency to radiant heat and paw withdrawal threshold to von Frey probes were measured. The first set of experiments examined the effects of tart cherry anthocyanins (400 mg/kg) on the nociceptive behaviors and edema associated with inflammation induced by intraplantar injection of 1% carrageenan. These studies also included tests of motor coordination. The second set of experiments determined if tart cherry anthocyanins (15, 85, and 400 mg/kg) dose-dependently affected the inflammation induced by intraplantar injection of 25% complete Freund's adjuvant. We found that tart cherry extracts reduce inflammation-induced thermal hyperalgesia, mechanical hyperalgesia and paw edema. The suppression of thermal hyperalgesia was dose-dependent and the efficacy of highest dose (400 mg/kg) was similar to indomethacin (5 mg/kg). The highest dose anthocyanin (400 mg/kg) had no effects on motor function. These data suggest that tart cherry anthocyanins may have a beneficial role in the treatment of inflammatory pain. The antihyperalgesic effects may be related to the anti-inflammatory and antioxidant properties of anthocyanins. A better understanding of the modulatory role of dietary constituents and phytonutrients on pain will offer further therapeutic options for treating patients with persistent and chronic pain conditions.

Administration, Oral↗

PubMed2004

Analgesic effects of a soy-containing diet in three murine bone cancer pain models.

UNLABELLED: Bone is a common metastatic site for prostate and breast cancer, and bone cancer is usually associated with severe pain. Traditional treatments for cancer pain can sometimes be ineffective or associated with side effects. Thus an increasing number of patients seek alternative therapies. In this study we investigated the analgesic effects of a soy diet on 3 experimental models of bone cancer pain. Mice were fed a diet in which the protein source was either soy or casein. After 1 week on the diet, sarcoma cells (NCTC 2472) were injected into the medullary cavity of the humeri, femur, or calcaneus. Experimenters blinded to diet of the animal assessed the pain behavior in these animals, forelimb grip force in the humerus model and paw withdrawal frequency to mechanical stimuli in the calcaneus and femur models. The effect of morphine on cancer-induced pain behavior was investigated in calcaneus and femur models. In addition, in the femur model, the effects of soy on tumor size and bone destruction were studied. The soy diet reduced secondary mechanical hyperalgesia in the femur model but had no effect on primary mechanical hyperalgesia in the calcaneus model or on movement-related hyperalgesia in the humerus model. No dietary impact was discerned in measurements of tumor size, bone destruction, and body weight in the femur model, suggesting that the soy diet had no effect on cancer growth. Morphine dose-dependently reduced hyperalgesia with no diet-based difference. These results suggest that a soy diet might provide analgesia in certain forms of hyperalgesia associated with bone cancer. PERSPECTIVE: The study raises the possibility of dietary supplements influencing aspects of cancer pain. Further research will help determine if use of nutritional supplements, such as soy proteins, can reduce opioid analgesic use in chronic pain states and help minimize the side effects associated with long term use of opioids.

Analgesics↗

PubMed2004

Antiallodynic effects of systemic and intrathecal morphine in the spared nerve injury model of neuropathic pain in rats.

BACKGROUND: The efficacy of opioids for neuropathic pain remains controversial. The effects of morphine on pain behavior were investigated in two animal models of neuropathic pain: the spared nerve injury (SNI) model and the spinal nerve ligation (SNL) model. METHODS: Nerve injuries were created in rats either by tight ligation and section of the left tibial and common peroneal nerves (SNI) or by unilateral ligation of L5 and L6 spinal nerves (SNL). Paw withdrawal threshold to mechanical stimuli was measured using the up-down method in the hairy and glabrous skin territories of the sural nerve for SNI rats or in the mid-plantar paw of SNL rats. RESULTS: Before SNI, the median paw withdrawal thresholds in hairy and glabrous skin were similar (26 g [25%, 75% quartiles: 26, 26 g]). The paw withdrawal threshold decreased after SNI in both hairy and glabrous skin (P < 0.001). Thirty days after the SNI, the threshold in hairy skin (0.3 g) was significantly lower than in glabrous skin (1.9 g; P < 0.001). In blinded experiments, both subcutaneous and intrathecal morphine (0.1-10 microg) dose-dependently attenuated mechanical allodynia induced by SNI measured in the hairy skin, an effect that was naloxone reversible. The ED50 for the intrathecal morphine was 0.52 microg (95% confidence interval, 0.31-0.90 microg). Morphine (1 microg intrathecal) attenuated SNI-induced mechanical allodynia in glabrous skin with potency similar to that in hairy skin. In SNL rats, morphine (30 microg intrathecal) almost completely reversed the SNL-induced mechanical allodynia. CONCLUSIONS: (1) SNI-induced mechanical allodynia is characterized by a lower paw withdrawal threshold in hairy versus glabrous skin; (2) systemic and intrathecal morphine reverse SNI-induced mechanical allodynia in a dose-dependent fashion; and (3) intrathecal morphine also reverses SNL-induced mechanical allodynia. These results suggest that intrathecal opioids are likely to be effective in the treatment of neuropathic pain.

Animals↗

PubMed2004

Nerve injury induces a tonic bilateral mu-opioid receptor-mediated inhibitory effect on mechanical allodynia in mice.

BACKGROUND: Mice lacking the mu-opioid receptor gene have been used to characterize the role of mu-opioid receptors in nociception and the analgesic actions of opioid agonists. In this study, the authors determined the role of mu-opioid receptors in neuropathic pain behaviors and the effectiveness of mu- and kappa-opioid receptor agonists on this behavior in mice. METHODS: The authors studied the behavioral responses of mu-opioid receptor knockout and wild-type mice to thermal and mechanical stimuli before and after neuropathic pain induced by unilateral ligation and section of the L5 spinal nerve. Response to mechanical stimuli was evaluated by determining the frequency of hind paw withdrawal to repetitive stimulation using a series of von Frey monofilaments. Thermal hyperalgesia was assessed by determining the paw withdrawal latencies to radiant heat and frequency of hind paw withdrawal to cooling stimuli. The effects of systemic morphine, the kappa-opioid agonist U50488H, and naloxone on responses to mechanical and thermal stimuli were also studied in spinal nerve-injured mice. RESULTS: After spinal nerve injury, wild-type mice developed increased responsiveness to mechanical, heat, and cooling stimuli ipsilateral to nerve injury. mu-Opioid receptor knockout mice not only had more prominent mechanical allodynia in the nerve-injured paw, but also expressed contralateral allodynia to mechanical stimuli. Hyperalgesia to thermal stimuli was similar between mu-opioid knockout and wild-type animals. Morphine decreased mechanical allodynia dose dependently (3-30 mg/kg subcutaneous) in wild-type mice--an effect that was attenuated in the heterozygous mice and absent in the homozygous mu-opioid knockout mice. The kappa-opioid agonist U50488H (3-10 mg/kg subcutaneous) attenuated mechanical allodynia in wild-type, heterozygous, and homozygous mu-opioid mice. Naloxone in wild-type mice resulted in enhanced ipsilateral and contralateral allodynia to mechanical stimuli that resembled the pain behavior observed in mu-opioid receptor knockout mice. CONCLUSIONS: The authors' observations indicate that (1) unilateral nerve injury induces a bilateral tonic activation of endogenous mu-opioid receptor-mediated inhibition that attenuates mechanical allodynia but not thermal hyperalgesia, (2) both mu- and kappa-opioid agonists attenuate neuropathic pain in mice, and (3) the antihyperalgesic actions of morphine are mediated primarily via mu-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2003

Impaired NMDA receptor-mediated postsynaptic function and blunted NMDA receptor-dependent persistent pain in mice lacking postsynaptic density-93 protein.

Modification of synaptic NMDA receptor (NMDAR) expression influences NMDAR-mediated synaptic function and associated persistent pain. NMDARs directly bind to a family of membrane-associated guanylate kinases (MAGUKs) that regulate surface and synaptic NMDAR trafficking in the CNS. We report here that postsynaptic density-93 protein (PSD-93), a postsynaptic neuronal MAGUK, is expressed abundantly in spinal dorsal horn and forebrain, where it colocalizes and interacts with NMDAR subunits NR2A and NR2B. Targeted disruption of the PSD-93 gene reduces not only surface NR2A and NR2B expression but also NMDAR-mediated excitatory postsynaptic currents and potentials, without affecting surface AMPA receptor expression or its synaptic function, in the regions mentioned above. Furthermore, mice lacking PSD-93 exhibit blunted NMDAR-dependent persistent pain induced by peripheral nerve injury or injection of Complete Freund's Adjuvant, although they display intact nociceptive responsiveness to acute pain. PSD-93 appears to be important for NMDAR synaptic targeting and function and to be a potential biochemical target for the treatment of persistent pain.

Animals↗