OBJECTIVETo investigate the effect of L-838,417 on the results of behavioral test in rats with experimentally induced trigeminal neuralgia.

METHODSMale SD rats were randomized into model group (n=34), sham-operated group (n=30) and control group (n=6). Thirty rats with trigeminal neuralgia induced by chronic constriction injury of the infraorbital nerve below the zygomatic bone were randomly divided into 5 equal groups for treatment with 1.0 mg/kg L-838,417 (L1 group), 10.0 mg/kg L-838,417 (L10 group), 5 mg/kg morphine (M group), 3 mg/kg diazepam (D group), or normal saline (NS group). The pain threshold of the tentacles pad to von-Frey filament stimulation was measured in the rats before and at 1, 2, 3, 4, 5 h after the treatments. The sedative effect of L-838,417 was evaluated by recording the position scores and righting reflex scores, and the drug tolerance was also evaluated.

RESULTSNine days after the operation, the pain threshold of the rats in the model group was significantly decreased compared with that before operation and that of the sham group (P<0.01). The threshold of L1 and L10 groups were both significantly increased 1 h after L-838,417 administration (P<0.01). The rats in the NS, L1, and L10 groups did not show unusual posture or righting reflex. In L1 and L10 groups, L838,417 did not show attenuated efficacy after prolonged use (10 days).

CONCLUSIONL-838,417 can effectively improve hyperalgesia in rats with trigeminal neuralgia without causing sedation, motor impairment, or drug tolerance.

Animals ; Fluorobenzenes ; pharmacology ; Hyperalgesia ; drug therapy ; Male ; Pain Measurement ; Pain Threshold ; drug effects ; Rats ; Rats, Sprague-Dawley ; Triazoles ; pharmacology ; Trigeminal Neuralgia ; drug therapy ; physiopathology

OBJECTIVE: To investigate the effects of ginsenoside-Rg on mechanical allodynia, heat hyperalgeia, depressive state of rats with chronic sciatic nerve constriction injury. METHODS: Fifty SD rats were randomly divided into 5 groups: blank control group (Normal, normal + saline),sham operation group (Sham, sham operation + saline),chronic constriction injury of the sciatic nerve group (CCI, CCI + saline),ginsenoside-Rg low dose group (CCI + Rg 5 mg/kg), and ginsenoside-Rg high dose group (CCI + Rg 10 mg/kg).After the CCI model was established,drug were injected into the abdominal cavity through the syringe once a day,for 14 consecutive days.The mechanical shrinkage foot reflex threshold (MWT) and thermal withdrawal latency(TWL) were determined at 1 d before the operation and at 1,3,5,7,10 and 14 d after the operation.Light-dark transition test, forced swimming test were determined at 1 d before the operation and at 14 d after the operation. RESULTS: Compared with the sham group, the MWL and TWL of the CCI rats were decreased significantly (P＜0.01), time in the light compartment and number of transition were decreased (P＜0.01), the immobility time in FST was also prolonged significantly (P＜0.01). At 14 days after CCI operation, the MWL and TWL of the ginsenoside-Rg groups were increased significantly (P＜0.01), time in the light compartment and number of transition were also shortened significantly (P＜0.01), the immobility time in FST was also shortened significantly (P＜0.01). CONCLUSION Intraperitoneal injection of ginsenoside-Rg can inhibit the mechanical and thermal pain sensitivity of CCI rats,and can relieve depressive state.
Animals ; Constriction ; Ginsenosides ; pharmacology ; Hot Temperature ; adverse effects ; Hyperalgesia ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; injuries

OBJECTIVE: To investigate the mechanisms underlying elemene-induced analgesia in rats with spared nerve injury (SNI). METHODS: Sixty-five rats were equally divided into 5 groups using a random number table: naive group, sham group, SNI group, SNI + elemene (40 mg·kg RESULTS: The SNI rat model exhibited a significant decrease in paw withdrawal threshold and exploratory behaviour in the EPM (P<0.05). Consecutive administration of elemene alleviated SNI-induced mechanical allodynia and anxiety in rats (P<0.05). Immunohistochemical data showed that elemene decreased SNI-induced upregulation of NDRG2 within the SDH (P<0.05). Double immunofluorescent staining data further showed that elemene decreased SNI-induced upregulation of the number of GFAP immunoreactive (-ir), NDRG-ir, and GFAP/NDRG2 double-labelled cells within the SDH (P<0.05). Immunoblotting data showed that elemene decreased SNI-induced upregulation of GFAP and NDRG2 within the SDH (P<0.05). CONCLUSION Elemene possibly alleviated neuropathic pain by downregulating the expression of NDRG2 in spinal astrocytes in a rat model of SNI.
Animals ; Astrocytes ; Disease Models, Animal ; Emulsions ; Hyperalgesia/drug therapy* ; Nerve Tissue Proteins ; Neuralgia/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Sesquiterpenes ; Spinal Cord ; Spinal Cord Dorsal Horn

Trigeminal neuralgia (TN) is a kind of recurrent transient and severe pain that is limited to the trigeminal nerve in one or more branches. The clinical incidence of TN is high, which seriously affects the quality of life of the patients and is difficult to cure. The present study investigated the effects of tetramethylpyrazine (TMP) on TN induced by chronic constriction injury of the infraorbital nerve (ION-CCI) in rats. Adult male Sprague-Dawley rats were randomly assigned to four groups: sham, sham treated with TMP (Sham+TMP), TN model (TN), and TN treated with TMP (TN+TMP). The rat TN model was established by ION-CCI and TMP (50 mg/kg) was injected intraperitoneally once a day for 2 weeks after operation. The mechanical response threshold was tested by the electronic von Frey filaments. The expression of CGRP in the trigeminal ganglia (TGs) of rats on the operative side was detected by RT-PCR, immunohistochemical staining and Western blot. In 15 days after operation, TN group showed a robust decrease in mechanical response threshold as compared with sham group. From day 9 to day 15 after operation, TMP treatment significantly suppressed the TN-induced mechanical hyperalgesia (P < 0.05). On day 15 after operation, RT-PCR, immunohistochemical staining and Western blot analysis showed an obvious increase in expression level of CGRP in TGs of TN group compared with sham group, which was downregulated by TMP treatment (P < 0.05). These results suggested that TMP might have a therapeutic potential for the treatment of TN through regulating CGRP expression in the TGs.
Animals ; Constriction ; Hyperalgesia ; drug therapy ; Male ; Pyrazines ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Trigeminal Ganglion ; physiopathology ; Trigeminal Neuralgia ; drug therapy

The use of opioids for the treatment of chronic non-cancer pain has become more widespread recently. Available data support the short-term use of opioids in clearly defined nociceptive and neuropathic pain states. Their use in 'pathological' pain states without a clear diagnosis, such as chronic low back pain, is more contentious. A decision to initiate opioid treatment in these conditions requires careful consideration of benefits and risks; the latter include not only commonly considered adverse effects such as constipation, but also opioid-induced hyperalgesia, abuse, addiction and diversion. Ideally, treatment goals should not only be relief of pain, but also improvement of function. Opioid treatment of chronic non-cancer pain requires informed consent by, and preferably a treatment contract with, the patient. Treatment should be initiated by a trial period with defined endpoints using slow-release or transdermal opioids. Ongoing management of the patient requires ideally a multi-disciplinary setting. Treatment should not be regarded as life-long and can be discontinued by tapering the dose.
Analgesics, Opioid ; adverse effects ; therapeutic use ; Humans ; Hyperalgesia ; chemically induced ; Low Back Pain ; drug therapy ; Pain, Intractable ; drug therapy ; Substance-Related Disorders ; prevention & control

OBJECTIVE: To investigate the effect of escin in relieving chemotherapy-induced peripheral neuropathic pain in rats and explore and the underlying mechanism. METHODS: Eighteen SD rats were randomly divided into 3 groups ( RESULTS: The rats in both the escin preconditioning group and escin postconditioning group showed obviously increased thresholds of mechanical allodynia and thermal hyperalgesia as compared with those in the control group ( CONCLUSIONS Escin can alleviate chemotherapy-induced peripheral neuropathic pain in rats possibly by upregulating the expressions of autophagy-related proteins in the spinal cord.
Animals ; Antineoplastic Agents/therapeutic use* ; Autophagy ; Escin/therapeutic use* ; Hyperalgesia/drug therapy* ; Mice ; Neuralgia/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Spinal Cord

Nefopam has a pharmacologic profile distinct from that of opioids or other anti-inflammatory drugs. Several recent studies demonstrate that nefopam has a mechanism of action similar to those of anti-depressants and anticonvulsants for treating neuropathic pain. The present study investigates the mechanical antiallodynic effect of nefopam using immunohistochemical study and western blot analysis in a rat neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve ligation and intrathecal catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the sham surgery group (group S). Nefopam, either 10 or 100 microg/kg (group N10 or N100, respectively), and normal saline (group C) were intrathecally administered into the catheter every day for 14 days. The mechanical allodynic threshold of intrathecal nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5. Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic adenosine monophosphate response element binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal nefopam reduced mechanical allodynia in a rat neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the transcription factors' mitogen-activated protein kinases in the spinal cord.
Analgesics, Non-Narcotic/administration & dosage ; Animals ; Dose-Response Relationship, Drug ; Hyperalgesia/*drug therapy/etiology/*physiopathology ; Injections, Spinal ; Male ; Nefopam/*administration & dosage ; Neuralgia/complications/*drug therapy/*physiopathology ; Pain Measurement/drug effects ; Pain Perception/*drug effects ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome

The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β adrenergic signaling in DRGs.
Adrenergic Agents ; pharmacology ; Animals ; Ganglia, Spinal ; drug effects ; Hyperalgesia ; drug therapy ; physiopathology ; Hypersensitivity ; drug therapy ; Male ; Maternal Deprivation ; Neurons ; drug effects ; Patch-Clamp Techniques ; methods ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Stress, Physiological ; physiology ; Visceral Pain ; chemically induced ; metabolism

To study the analgesic effect of chronic administration with ferulic acid, and preliminarily discuss its mechanism. Thermal hyperalgesia and mechanical allodynia tests were conducted to observe the analgesic effect of chronic administration with ferulic acid on CCI mice. The neurochemical detection method was applied to observe the effect chronic administration with ferulic acid on monoamine neurotransmitter and monoamine oxidase activity. Compared with the normal group, CCI mice showed notable reduction in heat sensation and nociceptive threshold in and mechanical allodynia. Ferulic acid (10, 20, 40 and 80 mg x kg(-1), po) could significantly reverse the situations. In an in-depth study, we found that the reason for these results was that ferulic acid was dose-dependent in increasing 5-HT and NE levels in hippocampus, frontal cortex and amygdale and could inhibit MAO-A activity in mouse brains. These results showed that ferulic acid has the analgesic effect. Its mechanism may be related to the inhibition of monoamine oxidase activity and the increase in monoamine neurotransmitter in mouse brains.
Analgesics ; administration & dosage ; Animals ; Behavior, Animal ; drug effects ; Coumaric Acids ; administration & dosage ; Humans ; Hyperalgesia ; drug therapy ; psychology ; Male ; Mice ; Mice, Inbred ICR ; Monoamine Oxidase ; metabolism ; Neurotransmitter Agents ; metabolism ; Sciatic Nerve ; drug effects ; injuries ; Sciatic Neuropathy ; drug therapy ; metabolism ; psychology

BACKGROUND: Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer. METHODS: Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat. RESULTS: Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats. CONCLUSIONS: Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain.
Acetone ; Animals ; Body Weight ; Cisplatin ; Drug Therapy ; Female ; Hot Temperature ; Humans ; Hyperalgesia ; Models, Animal* ; Neoplasm Metastasis ; Neuralgia* ; Peripheral Nervous System Diseases ; Rats* ; Rats, Sprague-Dawley