TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain

Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund’s adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol–induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol– and WS-12–induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects.     

气相色谱法测定强力枇杷露中薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱的含量

目的：建立气相色谱法同时测定强力枇杷露中薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱四种成分含量的方法。方法：试样用乙酸乙酯振摇提取,色谱柱为100%二甲基聚硅氧烷固定液的毛细管柱,柱温从100℃程序升温至270℃,保持20 min,检测器为 FID。结果：薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱在各自测定范围内有良好线性关系,各成分平均回收率（n=6）在96.76%~113.34%,RSD<6.0%。结论：本方法准确可靠,重现性好,可有效地控制强力枇杷露的质量。     

气相色谱法测定止痒洗剂中苯酚和薄荷脑的含量

目的建立气相色谱(GC)法测定止痒洗剂中苯酚和薄荷脑的含量方法,为止痒洗剂质量控制提供有效的分析手段。方法色谱柱:以HP-5(95%二甲基-5%二苯基聚硅氧烷,0.25 mm×30.0 m)毛细管柱为色谱柱;柱温为60℃;以8℃/min速率升温至160℃,保温10 min,进样口温度180℃,FID检测器,检测器温度300℃。空气流速为300 ml/min,分流比为20∶1。进样量1μl。结果苯酚和薄荷脑的线性范围分别是0.45～9 mg/ml和0.25～5 mg/ml,回归方程分别是A=1.476 9C-0.109 9(r=0.999 9)和A=1.393 7C-0.095 9(r=0.999 9)。苯酚和薄荷脑的平均回收率分别为100.6%(RSD=0.73%)和100.8%[相对标准偏差(RSD)=0.76%]。结论该方法简单,结果准确可靠,可用于止痒洗剂中苯酚和薄荷脑的含量测定。     

Inhibition of the shake response in rats by adenosine and 2-chloroadenosine

Shaking movements, similar to those made by a dog when wet, were elicited in rats by a) immersion in ice-water, b) injections of icilin, a chemical that produces sensations of cold, and c) naloxone-precipitated morphine withdrawal. Adenosine and 2-chloroadenosine produced dose-dependent inhibition of shaking to ice-water and icilin. The 2-chloroadenosine effect was mediated centrally because the ICV dose required to produce inhibition was not effective when given IP. Caffeine antagonized the inhibitory effects of adenosine and 2-chloroadenosine. 2-Chloroadenosine suppressed morphine-abstinence shaking as well as the body weight loss that normally accompanies withdrawal.     

负压穿刺改良术联合薄荷醇在小儿头皮静脉穿刺中的应用

目的 探讨负压穿刺改良术联合薄荷醇新型无痛消毒液应用于小儿头皮静脉穿刺中的临床效果.方法 将300例需静脉输液的患儿随机分为实验组与对照组,每组各150例.对照组采取常规小儿头皮静脉穿刺,实验组采取负压穿刺改良术联合薄荷醇新型无痛消毒液应用于小儿头皮静脉穿刺.比较两组穿刺时患儿疼痛的程度及一次穿刺的成功率.结果 实验组与对照组对穿刺时疼痛评分为0分的分别j为：85.3％,6.7％,两组患儿对穿刺时疼痛评分比较,有显著性差异（P＜0.01）;实验组和对照组一次性小儿头皮静脉穿刺成功率分别为96.7％和76.7％,两组患儿穿刺一次成功率比较,有显著性差-异-（P＜0.01）.结论 负压穿刺改良术联合薄荷醇新型无痛消毒液缓解患几静脉穿刺时的疼痛效果明显,小儿头皮静脉穿刺一次性成功率高,值得临床推广.     

薄荷药材的提取与含量测定

目的探讨建立薄荷药材的提取和含量测定方法。方法以薄荷脑为指标成分,采用DM—FFAP弹性石英毛细管柱,初始柱温为120℃,以2℃／min升温至140＇C,然后以15℃／min升温至220℃,保持5min。比较索氏提取、加热回流、超声提取法的差异,并优选最佳提取方法。结果最佳提取工艺：加10倍量无水乙醇溶液85℃回流提取1h。薄荷脑在34．034～343．04μg／ml浓度范围内线性关系良好,平均回收率为99．00％,RSD=1．87％（n=6）。结论本文所建立的提取和含量测定方法快速简便、结果可靠,可为薄荷药材质量控制提供科学依据。     

Split-dose menthol-enhanced PEG vs PEG-ascorbic acid for colonoscopy preparation

AIM:To compare the efficacy and palatability of 4L polyethylene glycol electrolyte(PEG)plus sugar-free menthol candy(PEG+M)vs reduced-volume 2 L ascorbic acid-supplemented PEG(Asc PEG).METHODS:In a randomized controlled trial setting,ambulatory patients scheduled for elective colonoscopy were prospectively enrolled.Patients were randomized to receive either PEG+M or Asc PEG,both splitdosed with minimal dietary restriction.Palatability was assessed on a linear scale of 1 to 5(1=disgusting;5=tasty).Quality of preparation was scored by assignment-blinded endoscopists using the modified Aronchick and Ottawa scales.The main outcomes were the palatability and efficacy of the preparation.Secondary outcomes included patient willingness to retake the same preparation again in the future and completion of the prescribed preparation.RESULTS:Overall,200 patients were enrolled(100patients per arm).PEG+M was more palatable than Asc PEG(76%vs 62%,P=0.03).Completing the preparation was not different between study groups(91%PEG+M vs 86%Asc PEG,P=0.38)but more patients were willing to retake PEG+M(54%vs 40%respectively,P=0.047).There was no significant difference between PEG+M vs Asc PEG in adequate cleansing on both the modified Aronchick(82%vs77%,P=0.31)and the Ottawa scale(85%vs 74%,P=0.054).However,PEG+M was superior in the left colon on the Ottawa subsegmental score(score0-2:94%for PEG+M vs 81%for Asc PEG,P=0.005)and received significantly more excellent ratings than Asc PEG on the modified Aronchick scale(61%vs 43%,P=0.009).Both preparations performed less well in afternoon vs morning examinations(inadequate:29%vs 15.2%,P=0.02).CONCLUSION:4 L PEG plus menthol has better palatability and acceptability than 2 L ascorbic acidPEG and is associated with a higher rate of excellentpreparations;Clinicaltrial.gov identifier:NCT01788709.     

毛细管气相色谱法测定复方薄荷脑滴鼻液中薄荷脑和樟脑的含量

目的建立毛细管气相色谱法测定复方薄荷脑滴鼻液中薄荷脑和樟脑的含量。方法采用毛细管气相色谱法,色谱柱为HP-INNOWAX(0.53mm×30m,1μm)弹性石英毛细管色谱柱,采用程序升温法,检测器温度为250℃,载气为N2,流速为5ml/min,进样口温度为200℃。结果薄荷脑和樟脑的回归方程分别为:Y=1.2286X-0.002214(r=0.9999),Y=1.2504X-0.002929(r=0.9999);线性范围分别为16.72~117.04μg·ml-1,17.52~122.64μg·ml-1,回收率分别为:101.5%,101.1%,RSD分别为0.40%、0.66%(n=10)。结论本法简便,快速,准确,可靠,适用于复方薄荷脑滴鼻液的质量控制。