OBJECTIVETo study the analgesic, antipyretic and anti-inflammatory effect of Bailian Caogen granule.

METHODThe antipyretic effects of Bailian Caogen granule was evaluated in rabbit fever model induced by peptone. The analgesic effect of the drug was studied with pain model of mice induced by acetic acid and hot plate, The severity of oedema in inflamed animal was observed to study the anti-inflammatory effects of Bailian Caogen granule.

RESULTBailian Caogen granule could obviously inhibit the fever of rabbits. The number of writhing induced by acetic acid was reduced and the pain threshold of mice was increased by Bailian Caogen granule. Bailian Caogen granule also had anti-inflammatory activity against xylene-induced mouse ear swelling and carrageenin-induced rat paw edema.

CONCLUSIONBailian Caogen granule has significant analgesic, antipyretic and anti-inflammatory activities.

Acetic Acid ; Analgesics, Non-Narcotic ; pharmacology ; Animals ; Body Temperature ; drug effects ; Coptis ; chemistry ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Edema ; pathology ; prevention & control ; Female ; Fever ; physiopathology ; prevention & control ; Glycyrrhiza uralensis ; chemistry ; Hot Temperature ; Hyperalgesia ; etiology ; physiopathology ; prevention & control ; Male ; Mice ; Pain ; chemically induced ; physiopathology ; prevention & control ; Pain Threshold ; drug effects ; Phellodendron ; chemistry ; Plants, Medicinal ; chemistry ; Pueraria ; chemistry ; Rabbits ; Random Allocation ; Rats ; Rats, Sprague-Dawley

The present study is to investigate whether the extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) signaling pathway contributes to the initiation of chronic constriction injury (CCI)-induced neuropathic pain in rats. Mechanical allodynia was assessed by measuring the hindpaw withdrawal threshold in response to a calibrated series of von Frey hairs. Thermal hyperalgesia was assessed by measuring the latency of paw withdrawal in response to a radiant heat source. The expressions of phosphor-ERK (pERK) and phosphor-CREB (pCREB) were examined using Western blot analysis and immunohistochemistry. An early robust increase in the expression of pERK on the spinal cords ipsilateral to injury was observed on day 1 after CCI, when the CCI-induced behavioral hypersensitivity had not developed yet. Moreover, the upregulation of pERK expression in ipsilateral spinal cord was associated with the increase in pCREB expression in bilateral spinal cord. Intrathecal administration of mitogen-activated protein kinase kinase (MEK) inhibitor U0126 before CCI can efficiently block and delay the CCI-induced mechanical allodynia and thermal hyperalgesia. These data suggest that activation of ERK and CREB in the spinal cord contributes to the initiation of peripheral nerve injury-induced pain hypersensitivity, and an early intervention strategy should be proposed.
Animals ; Butadienes ; pharmacology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Enzyme Inhibitors ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Hyperalgesia ; etiology ; physiopathology ; prevention & control ; Male ; Nitriles ; pharmacology ; Pain ; etiology ; physiopathology ; prevention & control ; Peripheral Nerve Injuries ; complications ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Sciatic Neuropathy ; metabolism ; physiopathology ; Spinal Cord ; metabolism

BACKGROUND/AIMS: Acidic saline injections produce mechanical hyperresponsiveness in male Sprague-Dawley rats. We investigated the effect of milnacipran in conjunction with tramadol on the pain threshold in an acidic saline animal model of pain. METHODS: The left gastrocnemius muscle of 20 male rats was injected with 100 microL of saline at pH 4.0 under brief isoflurane anesthesia on days 0 and 5. Rats administered acidic saline injections were separated into four study subgroups. After determining the pre-drug pain threshold, rats were injected intraperitoneally with one of the following regimens; saline, milnacipran alone (60 mg/kg), milnacipran (40 mg/kg) plus tramadol (20 mg/kg), or milnacipran (40 mg/kg) plus tramadol (40 mg/kg). Paw withdrawal in response to pressure was measured at 30 min, 120 min, and 5 days after injection. Nociceptive thresholds, expressed in grams, were measured with a Dynamic Plantar Aesthesiometer (Ugo Basile, Italy) by applying increasing pressure to the right or left hind paw until the rat withdrew the paw. RESULTS: A potent antihyperalgesic effect was observed when tramadol and milnacipran were used in combination (injected paw, p=0.001; contralateral paw, p=0.012). This finding was observed only at 30 min after the combination treatment. CONCLUSIONS: We observed potentiation of the antihyperalgesic effect when milnacipran and tramadol were administered in combination in an animal model of fibromyalgia. Further research is required to determine the efficacy of various combination treatments in fibromyalgia in humans.
Analgesics, Opioid/administration & dosage/*pharmacology ; Animals ; Antidepressive Agents/administration & dosage/*pharmacology ; Behavior, Animal/drug effects ; Cyclopropanes/administration & dosage/*pharmacology ; Disease Models, Animal ; Drug Synergism ; Drug Therapy, Combination ; Fibromyalgia/chemically induced/complications/*prevention & control ; Hydrogen-Ion Concentration ; Hyperalgesia/etiology/*prevention & control ; Injections, Intraperitoneal ; Male ; Pain/etiology/*prevention & control ; Pain Measurement ; Pain Threshold/*drug effects ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride ; Time Factors ; Tramadol/administration & dosage/*pharmacology

Citalopram and paroxetine are selective serotonin reuptake inhibitors and also have antinociceptive effects. We investigated the antiallodynic and antihyperalgesic effects of intrathecally administered morphine, citalopram, paroxetine, and combinations thereof, in a rat model in which peripheral inflammation was induced by complete Freund's adjuvant (CFA). Drugs were intrathecally administered via direct lumbar puncture. Mechanical allodynia was measured using a Dynamic Plantar Aesthesiometer. Thermal hyperalgesia and cold allodynia were determined by measuring latency of paw withdrawal in response to radiant heat and cold water. Behavioral tests were run before and 15, 30, 45, and 60 min after intrathecal injection. Intraplantar injection of CFA produced mechanical allodynia, thermal hyperalgesia, and cold allodynia. Intrathecally administered morphine (0.3 or 1 microg) had antiallodynic or antihyperalgesic effects (24.0%-71.9% elevation). The effects of morphine were significantly increased when a combination of citalopram (100 microg) and paroxetine (100 microg) was added (35.2%-95.1% elevation). This rise was reversed by naloxone and methysergide. The effects of citalopram and paroxetine were also reversed by naloxone and methysergide. We suggest that the mu opioid receptor and serotonin receptors play major roles in production of the antiallodynic and antihyperalgesic effects of morphine, citalopram, paroxetine, and combinations thereof, in animals experiencing inflammatory pain.
Analgesics, Opioid/administration & dosage/*pharmacology ; Animals ; Behavior, Animal/drug effects ; Citalopram/administration & dosage/pharmacology ; Disease Models, Animal ; Hyperalgesia/etiology ; Inflammation/*chemically induced/pathology ; Injections, Spinal ; Male ; Morphine/administration & dosage/*pharmacology ; Pain/*prevention & control ; Pain Measurement ; Pain Threshold/drug effects ; Paroxetine/administration & dosage/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin/*chemistry/metabolism ; Serotonin Uptake Inhibitors/administration & dosage/*pharmacology ; Temperature ; Time Factors