The Effect Of (+)-borneol In Chronic Pain

Pain,an unpleasant sensation that we all experience in daily life.It is an alert mechanism to prevent further or impending tissue injury.The word “pain” is commonly referred to conscious experiences associated with the potential injury of body or real injury of body,but also discomfort feelings.Pain is categorized as acute or chronic pain.Acute pain rarely needs medical attention.It is essential to an organism's survival and wellbeing,which is of ability to dectect noxious stimuli.Chronic pain persists long,which lasts three months or more than many years.Chronic pain is a major public health problem,with epidemiological studies.It is a disease about neuroal system,and the mechanisms are complicate.Chronic pain is a major public health problem,with epidemiological studies reporting about one fifth of the general population to be affected both in the USA and Europe.The condition is debilitating and causes not only considerable personal suffering but also enormous socioeconomic costs,estimated to reach an annual 60 billion U.S.dollars in lost productivity.Moreover,the figure is increasing.Chronic pain is categorized as inflammatory or neuropathic,each involving neuroplastic changes leading to hypersensitivity in both peripheral and central nociceptive system.Despite a lot of nonprescription analgesics being advertised and sold in drugstores,treatment of pain is still dominated by two classical medications: opioids and nonsteroidal anti-inflammatory drugs.However,these drugs are of adverse effects and insufficient effectiveness in many tupes of pain.Natural products with few side effects,such as monoterpenes,are emerging therapeutic resources for developing new drugs to treat chronic pain.Therefore,to find a safe and effective medicine is important.Central sensitization is important in the development and maintenance of chronic pain.After peripheral tissue or nerve injury,spinal cord dorsal horn inhibitory circuit is impaired,which serves as a key contributor to central sensitization.Loss of inhibition contributes not only to the development of spontaneous pain but also to the mechanical hypersensitivity(allodynia)and hyperalgesia.?-Aminobutyric acid(GABA)and glycine are the two fast inhibitory neurotransmitters in the mammalian spinal cord.Blocking spinal cord GABAergic neurotransmission by intrathecally injecting GABA receptor antagonist leads to hypersensitivity to innocuous stimuli.Drugs which activate GABAA receptors(GABAARs),such as GABAARs agonists or positive allosteric modulators benzodiazepines,have been proposed as potent analgesics in various models of inflammatory and neuropathic pain.(+)-Borneol,a bicyclic monoterpene alcohol,is present in the essential oil of medicinal plants.Natural borneol is(+)-borneol and is widely used in food and also used for analgesia and anaesthesia in traditional Chinese medicine.Recent studies reported that(+)-borneol has a variety of pharmacological effects,including anti-inflammatory and neuroprotective effects.Despite being used in pharmaceutical preparations to treat acute pain,little is known about the effect of(+)-borneol on chronic pain.In the present study,we investigated whether(+)-borneol produces anti-hyperalgesic effect in chronic inflammatory and neuropathic pain in rodents,and possible mechanisms underlying the anti-hyperalgesic effect.In part one,we used segmental spinal nerve ligation(SNL)to induce neuropathic pain.Throgh three drug administrations of intrathecal injection(i.t.)and intragastric administration(p.o.),and for different doses of(+)-borneol,we examined wheather(+)-borneol can reduce mechanical hypersensitivity dose-dependently in SNL models or not.In part two,we used intraplantar(i.pl.)injection of complete Freund's adjuvant(CFA)to induce inflammatory pain.Throgh two drug administrations of intrathecal injection(i.t.)and intragastric administration(p.o.),and for different doses of(+)-borneol,we examined wheather(+)-borneol can reduce mechanical hypersensitivity dose-dependently in CFA models or not.In part three,in physiological condition,through intrathecally injercting GABAA receptor antagonist bicuculline,we examined wheather bicuculline can reduce mechanical hypersensitivity;then through intrathecally injercting(+)-borneol,we examined wheather(+)-borneol can increase mechanical hypersensitivity.At last,we examined whether the anti-hyperalgesic effects of(+)-borneol are abolished by a selective GABAA receptor(GABAAR)antagonist bicuculline(i.t.,at 30 min after(+)-borneol injection)in SNL or CFA models.In part four,we examined motor performance in rotarod test and spontaneous locomotor activity in open field test.In conclusion,(+)-borneol has remarkable anti-hyperalgesic effects on neuropathic and inflammatory pain in animal models.It may ameliorate mechanical hyperalgesia by enhancing GABAAR-mediated GABAergic transmission in the spinal cord.In addition,motor function and locomotor activity are not effected by (+)-borneol.Therefore,(+)-borneol could serve as a therapeutic for chronic pain.