piperine and Pain

Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (P<0.01) the acetic acid-induced writhing in mice, similar to the effect of indomethacin (20 mg/kg i.p.). In the tail flick assay, piperine (30 and 50 mg/kg, i.p.) and morphine (5 mg/kg, i.p.) caused a significant increase (P<0.01) in the reaction time of mice. Pre-treatment of animals with naloxone (5 mg/kg i.p.), reversed the analgesic effects of both piperine and morphine in the tail flick assay. Piperine (30, 50 and 70 mg/kg, i.p.) and standard drugs, valproic acid (200 mg/kg, i.p.), carbamazepine (30 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) significantly (P<0.01) delayed the onset of PTZ-and PIC-induced seizures in mice. These findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively. Moreover, piperine being the main constituent of black pepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.

Topics: Acetic Acid; Alkaloids; Analgesics; Animals; Anticonvulsants; Benzodioxoles; Hot Temperature; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Pentylenetetrazole; Picrotoxin; Piper nigrum; Piperidines; Polyunsaturated Alkamides; Seizures

TRPV1 (transient receptor potential vanilloid 1) is a ligand-gated ion channel expressed predominantly in nociceptive primary afferents that plays a key role in pain processing. In vivo activation of TRPV1 receptors by natural agonists like capsaicin is associated with a sharp and burning pain, frequently described as pungency. To elucidate the mechanisms underlying pungency we investigated a series of TRPV1 agonists that included both pungent and non-pungent compounds covering a large range of potencies. Pungency of capsaicin, piperine, arvanil, olvanil, RTX (resiniferatoxin) and SDZ-249665 was evaluated in vivo, by determining the increase in the number of eye wipes caused by direct instillation of agonist solutions into the eye. Agonist-induced calcium fluxes were recorded using the FLIPR technique in a recombinant, TRPV1-expressing cell line. Current-clamp recordings were performed in rat DRG (dorsal root ganglia) neurons in order to assess the consequences of TRPV1 activation on neuronal excitability. Using the eye wipe assay the following rank of pungency was obtained: capsaicin>piperine>RTX>arvanil>olvanil>SDZ-249665. We found a strong correlation between kinetics of calcium flux, pungency and lipophilicity of TRPV1 agonists. Current-clamp recordings confirmed that the rate of receptor activation translates in the ability of agonists to generate action potentials in sensory neurons. We have demonstrated that the lipophilicity of the compounds is directly related to the kinetics of TRPV1 activation and that the latter influences their ability to trigger action potentials in sensory neurons and, ultimately, pungency.

Topics: Action Potentials; Alkaloids; Animals; Benzodioxoles; Capsaicin; Diterpenes; Ganglia, Spinal; Kinetics; Lipid Metabolism; Male; Neurons, Afferent; Pain; Patch-Clamp Techniques; Piperidines; Polyunsaturated Alkamides; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Sensory Receptor Cells; Solubility; TRPV Cation Channels; Urea

Bioactivity guided isolation of the bark of Careya arborea afforded piperine--an alkaloid chemically known as 1-[5-(1,3-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine, which was found to possess significant central and peripheral analgesic activity. At oral doses of 10, 20 and 30 mg/kg body weight, piperine exhibited 41 (p < 0.01), 45 (p < 0.01) and 53% (p < 0.001) inhibition of acetic acid induced writhing in mice respectively. At doses of 20 and 30 mg/kg body weight, the compound also showed 31.8 (p < 0.05) and 52.4% (p < 0.01) prolongation of tail flicking time of mice 30 min after the treatments determined by the radiant heat method.

Topics: Acetic Acid; Alkaloids; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bangladesh; Behavior, Animal; Benzodioxoles; Female; Lecythidaceae; Magnetic Resonance Spectroscopy; Male; Mass Spectrometry; Mice; Pain; Pain Measurement; Piperidines; Plant Epidermis; Plant Extracts; Polyunsaturated Alkamides; Reaction Time

Contraction of the isolated tracheal strip to capsaicin was prevented by chronic denervation of the tissue. Tetrodotoxin, hyoscine and hexamethonium caused no inhibition of the response, suggesting that tetrodotoxin-resistant terminal portions of non-cholinergic nerves were activated in this way. There was a strong correlation between the pain-producing and tracheoconstrictor effects of piperine, pungent and non-pungent capsaicin congeners. Common site of action was evidenced by crossed tachyphylaxis. It is concluded that the capsaicin-sensitive sensory nerve endings have a dual sensory-efferent function. Excitation-secretion coupling in this system could operate without an axon reflex.

Topics: Alkaloids; Animals; Benzodioxoles; Capsaicin; Denervation; Dose-Response Relationship, Drug; Drug Interactions; Guinea Pigs; Muscle, Smooth; Neuromuscular Junction; Pain; Piperidines; Polyunsaturated Alkamides; Tetrodotoxin; Trachea