Cold Sensation Research Articles

The Effectiveness of Topical Cannabidiol Oil in Symptomatic Relief of Peripheral Neuropathy of the Lower Extremities.

Peripheral neuropathy can significantly impact the quality of life for those who are affected, as therapies from the current treatment algorithm often fail to deliver adequate symptom relief. There has, however, been an increasing body of evidence for the use of cannabinoids in the treatment of chronic, noncancer pain. The efficacy of a topically delivered cannabidiol (CBD) oil in the management of neuropathic pain was examined in this four-week, randomized and placebocontrolled trial. In total, 29 patients with symptomatic peripheral neuropathy were recruited and enrolled. 15 patients were randomized to the CBD group with the treatment product containing 250 mg CBD/3 fl. oz, and 14 patients were randomized to the placebo group. After four weeks, the placebo group was allowed to crossover into the treatment group. The Neuropathic Pain Scale (NPS) was administered biweekly to assess the mean change from baseline to the end of the treatment period. The study population included 62.1% males and 37.9% females with a mean age of 68 years. There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study. Our findings demonstrate that the transdermal application of CBD oil can achieve significant improvement in pain and other disturbing sensations in patients with peripheral neuropathy. The treatment product was well tolerated and may provide a more effective alternative compared to other current therapies in the treatment of peripheral neuropathy.

Comparison of the effectiveness of circumferential versus non-circumferential spread in median and ulnar nerve blocks. A double-blind randomized clinical trial

Background and objectivesCircumferential (C) spread of local anesthetic around the nerve is recommended for a successful nerve block. We tested the hypothesis that C spread produces a more complete block...

Brief analysis of the relationship between "sasa zhenhan" of foot-yangming stomach-meridian syndrome and stomach

"Sasa zhenhan" is a word describing the syndrome of cold sensation, which is one of the foot-yangming stomach-meridian syndromes. The lesions of stomach and yangming meridian could cause changes of yang qi and superficial symptoms of the interior syndrome, leading to "sasa zhenhan". In this study, the specific manifestation of the "sasa zhenhan" is analyzed from the aspect of word meaning, and the relationship between the "sasa zhenhan" and stomach is further discussed through the perspectives of yang qi and the exterior-interior relationship. In addition, combined with typical clinical case, it is suggested that attention should be paid on the relationship between exterior and interior syndromes, and the clinical application of tongfu and tongyang method (activating yang qi and promoting qi circulation of fu organs) should be strengthened, which could expand the new thinking of clinical treatments for viscera diseases through acupuncture and moxibustion.

N-glycosylation state of TRPM8 protein revealed by terahertz spectroscopy and molecular modelling

TRPM8 member of the TRP superfamily of membrane proteins participates to various cellular processes ranging from Ca2+ uptake and cold sensation to cellular proliferation and migration. TRPM8 is a large tetrameric protein with more than 70% of its residues located in the cytoplasm. TRPM8 is N-glycosylated, with a single site per subunit. This work focuses on the N-glycosylation of TRPM8 channel that was previously studied by our group in relation to proliferation and migration of tumoral cells. Here, experimental data performed with deglycosylating agents assess that the sole glycosylation site contains complex glycans with a molecular weight of 2.5 kDa. The glycosylation state of TRPM8 in cells untreated and treated with a deglycosylating agent was addressed with Terahertz (THz) spectroscopy. Results show a clear difference between cells comprising glycosylated and deglycosylated TRPM8, the first presenting an increased THz absorption. Human TRPM8 was modelled using as templates the available TRPM8 and other TRPM channels structures. Glycosylations were modelled by considering two glycan structures with molecular weight close to the experiment: shorter and branched at the first sugar unit (glc1) and longer and unbranched (glc2). Simulation of THz spectra based on the molecular dynamics of unglycosylated and the two glycosylated TRPM8 models in lipid membrane and solvation box showed that glycan structure strongly influences the THz spectrum of the channel and of other components from the simulation system. Only spectra of TRPM8 with glc1 glycans were in agreement with the experiment, leading to the validation of glc1 glycan structure.

Discrimination of prediction models between cold-heat and deficiency-excess patterns

ObjectiveThe purpose of this study was to extract important patient questionnaire items by creating random forest models for predicting pattern diagnosis considering an interaction between deficiency-excess and cold-heat patterns. DesignA multi-centre prospective observational study. SettingParticipants visiting six Kampo speciality clinics in Japan from 2012 to 2015. Main outcome measureDeficiency–excess pattern diagnosis made by board-certified Kampo experts. MethodsWe used 153 items as independent variables including, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We sampled training data with an equal number of the different patterns from a 2 × 2 factorial combination of deficiency–excess and cold–heat patterns. We constructed the prediction models of deficiency–excess and cold–heat patterns using the random forest algorithm, extracted the top 10 essential items, and calculated the discriminant ratio using this prediction model. ResultsBMI and blood pressure, and subjective symptoms of cold or heat sensations were the most important items in the prediction models of deficiency–excess pattern and of cold–heat patterns, respectively. The discriminant ratio was not inferior compared with the result ignoring the interaction between the diagnoses. ConclusionsWe revised deficiency–excess and cold–heat pattern prediction models, based on balanced training sample data obtained from six Kampo speciality clinics in Japan. The revised important items for diagnosing a deficiency–excess pattern and cold–heat pattern were compatible with the definition in the 11th version of international classification of diseases.

Esant TH4 sindromo požymiams, stuburo mobilizacija veiksmingiau mažina rankų ir kaklo skausmą bei gerina funkciją nei savimobilizacija

Tyrimo pagrindimas. Pasireiškus Th4 sindromui, sutrinka vegetacinės nervų sistemos (VNS) funkcija (Karas, Pannone, 2017). Tai būklė, kuri gali atsirasti, kai kaklinės ir krūtininės stuburo dalies slanksteliai yra hipomobilūs, ir tai gali sukelti rankų parestezijas, tirpimą, šalimą arba prakaitavimą. Esant Th4 sindromui, gali sutrikti rankų judesių valdymas, atsirasti sunkumas, patinimas. Rankų skausmai gali būti susiję su sąstingiu ir galvos skausmu. Skausmas ir sąstingis pasireiškia menčių srityje, priekinėje arba nugarinėje krūtinės dalyje (Fernández-de-las-Peñas et al., 2015; Conroy, Schneiders, Tyrimo tikslas – įvertinti krūtininės stuburo dalies mobilizacijos ir savimobilizacijos poveikį rankų ir kaklo skausmui, funkcijai bei gyvenimo kokybei esant Th4 sindromo Metodai. Buvo tiriama 20 asmenų, kurie skundėsi galvos, rankų, pečių srities skausmu bei tirpimu. Buvo įvertinti pokyčiai miotomose ir dermatomose, rankų refleksai ir judesių amplitudės, rankų raumenų jėga, skausmas, Rezultatai. Tyrimo rezultatai parodė, kad MOB grupės kaklo srities ir rankų skausmas po mobilizacijos sumažėjo nuo 4,8 ± 1,55 iki 3,3 ± 0,71 (p < 0,05) ir nuo 4,5 ± 0,71 iki 2,8 ± 1,34 (p < 0,05). SAVIMOB grupės kaklo ir rankų skausmas po savimobilizacijos sumažėjo nuo 3,6 ± 0,84 iki 2,3 ± 1,7 (p > 0,05) ir nuo 4 ± 1,56 iki 3 ± 2,49 (p > 0,05). Po mobilizacijos nustatyta, kad iš visų gyvenimo kokybės rodiklių labiausiai pagerėjo socialinis funkcionavimas, fizinė būklė, sumažėjo kūno skausmai ir veiklos apribojimas dėl emocinių ir fizinių Išvados. Kineziterapija, kurios metu taikoma mobilizacija, veiksmingiau mažina kaklo ir rankos skausmą, turi tendenciją labiau pagerinti stuburo paslankumą ir gyvenimo kokybę nei kineziterapija, kai atliekama savimobilizacija.Raktažodžiai: Th4 sindromas, krūtininės stuburo dalies mobilizacija, savimobilizacija.

Diagnosis of the Trigeminal Nerve Injury in a Patient with Pontine Hemorrhage.

Herein, we present a patient who was diagnosed with trigeminal nerve injury following a pontine hemorrhage. A 38-year-old male was diagnosed with a left pontine hemorrhage and underwent conservative management at the neurosurgery department of a university hospital. After hemorrhage onset, he felt facial pain on the right side. After seven years, he visited the rehabilitation department of another hospital for evaluation of his right facial pain. He complained of somatosensory impairment and facial pain (tingling and cold sensation) on the right side as well as difficulty chewing and gait disturbance. On neurological examination, decreased touch sensation (approximately 30%) was observed on the right side of the face, in the oral cavity, and on the tongue (anterior two-thirds) as well as weakness of the right-sided masseter muscles. He also exhibitedallodynia without dysesthesia on the right side of the face. Diffusion tensor tractography showed the right trigeminal nerve to be discontinued at the anterior margin of the pons (arrow) compared to the state of the left trigeminal nerve.

Effects of Curcumin on Biological Behavior and NF-κB/TNF-α Pathway in Mice with Metastatic Bone Pain of Breast Cancer Induced by Walker 256 Cells

Background. The active ingredient curcumin of traditional Chinese medicine was selected as the research object to investigate the possible mechanism of breast cancer metastatic bone pain in mouse walker 256 cells and the effect of curcumin on the NF-κB/TNF-α pathway in order to provide a new idea for clinical treatment of breast cancer metastatic bone pain. Methods. By establishing an animal model of breast cancer bone metastasis in walker 256 cells, the biological behavior of nude mice was observed on the 8th day after successful modeling. Meanwhile, the low dose group, middle dose group and high dose group of mice were given 15 mg/kg, 25 mg/kg, 50 mg/kg of curcumin solution intraperitoneally in 21 days, and the right cavity bone and spinal cord distended in mice (L4-L6) tissues were used to detect related factors, Immunohistochemical method was used to detect c-fos in spinal cord. Expression levels of RANK, NF-κB and TNF-α were detected by RT-PCR and Western blot. Meanwhile, serum levels of Cox2, il-6, leukotriene and PGE2 were detected. Results. Observing the biological behavior index of nude mice, we found that the mechanical pain and thermal pain threshold decreased (p Conclusions. On the 8th day after the success of the animal model of breast cancer bone metastasis in Walker 256 cells, abnormal biological behaviors such as heat pain, cold pain sensation and spontaneous hyperalgesia were observed. Further studies have found that the increased expression of rank on osteoclasts induced up-regulated expression of NF-κB and c-fos, induced expression of TNF-α gene, and could induce synthesis and release of leukotriene, PGE2 through direct activation of cyclooxygenase, inflammatory media IL-6 cascade reaction, resulting in pathological pain and hypersensitivity. Traditional Chinese medicine active ingredient curcumin could reduce RANK expression of osteoclast, inhibit cell NF-κB and spinal cord c-fos activity, reduce TNF-α expression, inhibit Cox2 activity, and reduce the synthesis and release of inflammatory factors leukotriene and PGE2, thus exerting its analgesic effect, which provides new ideas and methods for clinical treatment of metastatic bone pain in breast cancer.

Evaluation of segmental epidural blockade following standard test dose versus test dose with addition of saline in abdominal surgeries.

Background and Aims:Epidural analgesia is widely used for pain relief but confirmation of accurate epidural placement is poorly understood. We proposed that sensory blockade to cold sensation would predict the accurate placement of epidural. The primary outcome was the assessment of sensory blockade at 5 and 10 min with a standard epidural test dose versus test dose with additional saline. We looked at haemodynamic changes following administration as secondary outcomes.Methods:Following Ethics Committee approval, 161 patients presenting for elective abdominal surgery needing epidural analgesia with general anaesthesia were randomly allocated into Group 1 receiving standard test dose (3 ml of 2% lignocaine with 1:2,00,000 adrenaline) or Group 2 (standard test dose with 6 ml of saline) epidurally. The blockade to cold sensation was assessed at 5 and 10 min. The heart rate (HR), systolic blood pressure (SBP), and mean arterial pressure (MAP) were recorded at baseline, 1, 5, and 10 min following epidural dosing. Statistical analysis was performed with Chi-square test for categorical and Student's t-test for continuous variables.Results:The sensory blockade at 5 min was 69.5% versus 82.3% (P = 0.059), and at 10 min 85.4% versus 97.5% (P = 0.01) in Groups 1 and 2, respectively. The MAP at 5 min (P = 0.032) and the HR and MAP at 10 min (P = 0.015, 0.04) were significantly lower in Group 2.Conclusion:An epidural test dose of 3 ml followed by additional 6 ml saline accurately predicted sensory blockade to cold at 10 min in comparison to the standard dose of 3 ml but was associated with a decrease in the HR and MAP.

Apical root canal cleaning after preparation with endodontic instruments: a randomized trial in vivo analysis.

ObjectivesThis study aimed to evaluate vital pulp tissue removal from different endodontic instrumentation systems from root canal apical third in vivo.Materials and MethodsThirty mandibular molars were selected and randomly divided into 2 test groups and one control group. Inclusion criteria were a positive response to cold sensibility test, curvature angle between 10 and 20 degrees, and curvature radius lower than 10 mm. Root canals prepared with Hero 642 system (size 45/0.02) (n = 10) and Reciproc R40 (size 40/0.06) (n = 10) and control (n = 10) without instrumentation. Canals were irrigated only with saline solution during root canal preparation. The apical third was evaluated considering the touched/untouched perimeter and area to evaluate the efficacy of root canal wall debridement. Statistical analysis used t-test for comparisons.ResultsUntouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.ConclusionsHero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during in vivo instrumentation is not entirely removed.

Correlation of Hand Ischemic Questionnaire with Digital Brachial Index In Patient with Upper Arm Native Arteriovenous Fistula

Introduction: Steal syndrome is one of the most feared complications in maintaining arteriovenous fistula (AVF) for hemodialysis. The incidence of steal syndrome in worldwide is estimated to be 0.5-5%. There are various non-invasive examinations to assess the degree of stealing, one of which is the digital brachial index (DBI). In this study, subjects with brachiocephalic AVF were assessed by the hand ischemic questionnaire (HIQ) to assess the manifestations of steal syndrome complained by the patient, which are the sensation of cold, pain, the decrease in sensation and strength, and cramps. The literature about the correlation of DBI with other assessment is still limited. Method: The subjects of this study were all patients undergoing hemodialysis with upper arm AVF at Cipto Mangunkusumo Hospital in the period May – June 2019. Patients will be asked about various symptoms of stealing syndrome, the severity, and also frequency, according to HIQ. The scores were then calculated, followed by scores of DBI measurements using a plethysmograph. The DBI values that considered to be meaningful as stealing syndrome were <0.6. The correlation between the two parameters was then analyzed. Results: From demographic data, characteristics of patients with native AVF by sex were 37 (46.2%) men and 43 (53.8%) women with an average age of 53 years. The minimum value of the HIQ score was 0, and the maximum value was 70, with a median value of 3. The correlation test between the total value of the HIQ questionnaire score and the DBI value found a significant correlation (r = -0.0798, p <0.001). A diagnostic tests was performed between HIQ scores using a cut-off value ≥50 with a DBI value <0.6 as a reference. It was obtained a sensitivity value of 15.3% and a specificity value of 100%, with a diagnostic accuracy of 58.75%. Conclusion: There was a good correlation between HIQ and DBI in patients undergoing hemodialysis using upper arm native AVF. The use of HIQ as a screening tool in native upper arm AVF patients is less recommended, but its use for patients who are suggestive of stealing syndrome has good specificity results. Keywords: digital brachial index, hand ischemic questionnaire, native arteriovenous fistula upper arm.

ГЕНЕЗИС ТА ОСОБЛИВОСТІ ФОРМУВАННЯ БАЗОВИХ МОДЕЛЕЙ ІДЕНТИФІКАЦІЇ КОЛЬОРУ

Purpose. The determination of the formation features of basic models of color and identification of color in the initial stages (the 18th – 19th centuries) of scientific research of the problem. Methodology of the research is based on historical and cultural method. The source base is the artistic, scientific and technical literature of the studied period and also artefacts. Results. This publication reveals a generalized approach to theoretical developments on color perception and identification, and covers the initial period of color research and the formation of basic models of color (the 18th – 19th centuries). So in the middle of the 17th century I. Newton founded a seven-color ordering model, placing them to a closed color circle. At about the same time, other attempts at color systemization were proposed, such as color identification in the form of tables of existing paints, the work of I. Brennen and R. Waller. Subsequently, Jacob Christoph Le Blon concluded that in order to get results, you could use only three colors, namely red, yellow and blue. Based on this work, M. Harris presented his color circle, J. Lambert – a triangular color pyramid, and Ph.Runge built a color sphere using the principle of the globe. Goethe, contrary to Newton's physical doctrine of colors, conceived another system, it was based on the phenomenological perception of color. According to Goethe and his followers, the colors come from the struggle of "light" and "darkness". A. Schopenhauer took the step that J. Goethe lacked in his thinking: A. Schopenhauer formed a doctrine of color in terms of psychology, noting the enormous role that our brain plays in color perception, and proposing his model of identification by the principle of intensity / extensiveness/quality. for the formal description of the tri-color system of color, forming a mathe-confirmation of T. Young's theory and came to the conclusion that for the comparison of all shades, three light sources were needed and sufficient: in the red, green and blue parts of the spectrum. The perception of other colors is conditioned by the interaction of these constituents. In his work, J. Maxwell proved that all colors come from a mixture of three spectral colors: red, green, and blue. Based on his research, he introduced the first two-dimensional color spectrum visualization system. H. Grassmann's merit is the mathematical representation of the three spectral colors. E. Hering's theory highlights the psychological aspects of color vision: warm sensations occur for white, yellow, and red colors, while cold sensations occur for black, dark blue, and light blue. G. Peano introduced the concept of "color space" as a system of vector space equations.

Reduced TRPM8 expression underpins reduced migraine risk and attenuated cold pain sensation in humans

Multiple genome-wide association studies have identified non-coding single-nucleotide variants (SNVs) near (e.g., rs10166942[C]) or within (rs17862920[T]) the TRPM8 gene that encodes a cold thermosensor is associated with reduced migraine risk. Furthermore, rs10166942[C]) and rs10166942[T]) are more prevalent in populations that reside in hotter and colder climates, respectively. Here we assessed whether these alleles affect TRPM8 expression in humans and human physiologic responses to cold challenge. Here we show that TRPM8 expression is decreased from the chromosome harboring the rs10166942[C] allele in the human dorsal root ganglia. Moreover, carriers of rs10166942[C] required significantly lower temperatures and longer duration of exposure to reach a cold pain threshold (CPTh), which correlated with decreased TRPM8 expression expected in the carriers. This study provides evidence for a genotype-dependent influence on cold pain sensation suggesting that carriers of the reduced migraine risk allele have reduced sensitivity to cold stimuli and that TRPM8 acts as a cold thermosensor and cold pain transducer in humans. Reduced TRPM8 expression and function underpins the migraine protection in carriers of rs10166942[C]; thus, the evaluation of TRPM8 antagonists as migraine therapeutics is warranted. Furthermore, these results provide mechanistic insights for evolutionary positive selection of rs10166942[T] allele in adaptation along latitudinal cline to colder climates.

Contact lens and eye glass wearers with and witouth ocular symptoms: differences in corneal sensitivity, blinking, tearing and corneal surface temperature

AbstractPurposeTo analyze corneal sensitivity, blink frequency (BF), tearing rate (TR), TBUT, and corneal surface temperature (CST) in young contact lens (CLs) and eye glass (EGs) wearers with and without ocular discomfort symptoms.MethodsEGs (n = 18) and CLs (n = 23) young subjects (18–40 years old, both sexes) participated voluntarily. CLs were classified as asymptomatic (A) or symptomatic (S) depending on their OSDI score (< 13 or ≥ 13, respectively). Corneal sensitivity to mechanical and chemical air puffs (3s duration, applied with a gas esthesiometer) and cold (4°C) saline drops was explored. Sensations evoked by each stimulus was scored with 0 to 10 VAS. BR (1 min at rest or during a task), TR (mm of wet phenol red threads, 15 s), TBUT (s), and CST (IR video thermography) were also measured.ResultsVAS values of irritation sensation evoked by mechanical and chemical stimulation (p < 0.05) were higher in CLs than in EGs while VAS values of cold sensation evoked by saline drops were similar in both groups. Although CST and TR were similar in EGs and CLs, TBUT was significantly shorter (p < 0.001) and BR was higher in CLs both at rest (p < 0.001) and during a visual task (p < 0.01). Although VAS values scored to corneal mechanical, chemical and cold stimulation were lower in CL‐S than in CL‐A, no differences were found in BR at rest or during the task, TR, TBUT and CST. Corneal sensitivity and CST were also similar in EG‐A and EG‐S, although TR (p < 0.05) and BF at rest (p < 0.05), but not during the task, were higher in EG‐S.ConclusionsResults show a reduced corneal sensitivity in symptomatic CL wearers, which suggests that corneal sensory nerve activity must be altered in a different degree in asymptomatic and symptomatic individuals, thus leading to changes in tearing and blinking regulation.Support: AEI‐ERDF SAF‐2017‐83674‐C2‐1‐R and 2‐R

Abstract 104: Metabolic Effect of Temperature Manipulation in Healthy Individuals

Introduction: Temperature manipulation to decrease metabolism is commonly after acute brain injury. Preclinical data suggest metabolism decreases 7-8% for each degree C drop in core temperature. We hypothesized similar results would be found in healthy individuals. Methods: Following informed consent and physical screening, we administered a 1mcg/kg bolus of dexmedetomidine followed by 20cc/kg of cold (4C) saline bolus. We cooled subjects using surface pads (emcools (Austria)). Dexmedetomidine infusion was titrated to effect (max dose <1.5mcg/kg/hr). We recorded vital signs, Richmond Agitation Sedation Scale, Bedside Shivering Assessment Scale and sensation of cold every 15 minutes. We measured resting metabolism at baseline and after each 1 C decrease in temperature thereafter using indirect calorimetry and a ventilated canopy system. We analyzed data using analysis of variance. Results: Median age in the 9 enrolled subjects was 30 (SD 10) years and most (78%) were male. Median height was 173 (IQR 168, 180) cm and median weight was 77 (IQR 72, 83) kg. Baseline VO2 was 3.4 (IQR 3.0, 3.8) ml/kg/min and baseline energy expenditure was 1692 (IQR 1579, 1845) kcal/day. Both VO2 and energy expenditure decreased with core temperature (p=0.017 and p=0.027) (Table). Conclusion: Metabolic rate decreases with core temperature manipulation. The largest change occurs between 37C and 36C with smaller changes thereafter.

Menthol as an Adjuvant to Help Athletes Cope With a Tropical Climate: Tracks From Heat Experiments With Special Focus on Guadeloupe Investigations.

Endurance and prolonged exercise are altered by hot climate. In hot and dry climate, thermoregulation processes, including evapotranspiration, normally maintain a relatively constant body core temperature. In hot and wet climate (usually called “tropical”), the decrease in evapotranspiration efficacy increases the sweating rate, which can rapidly induce severe hypohydration without efficiently reducing core temperature. The negative effects of tropical environment on long-duration exercise have been well documented, with clear demonstrations that they exceed the acclimation possibilities: both acclimated athletes and natives to tropical climate show impaired performances compared with that in neutral climate. New countermeasures, applicable during competitive events, are therefore needed to limit these negative effects. We studied the effects of several countermeasures in outdoor or natural tropical climates and noted that the easiest method to apply is cooling with cold (−1 to 3°C) beverage. Moreover, adding menthol increased the cold sensation induced by the beverage temperature, optimizing the positive effects on performance. We also demonstrated that efficient pre-cooling with cold menthol beverage requires drinking for 1 h instead of 30 min before the exercise. The optimal cooling method seems to be 1 h of cold + menthol pre-cooling ingestion followed by menthol + ice-slurry per-cooling. However, limitations should be noted: (1) the menthol concentration seems to be crucial, with positive effects for a 0.05% solution, whereas higher concentrations need to be explored; and (2) because it acts as a cold adjuvant without decreasing core temperature, menthol can lead to decreased thermoregulatory processes, thus inducing hyperthermia. Last, if menthol is added to cooling processes, athletes should first test them in training conditions for the maximal cooling effect to ensure optimal performance in competition in tropical climate.

Dietary Menthol Attenuates Inflammation and Cardiac Remodeling After Myocardial Infarction via the Transient Receptor Potential Melastatin 8.

Transient receptor potential melastatin subtype 8 (TRPM8) is a cold-sensing cation channel, mainly localized in the sensory neurons, which can be activated by menthol, a compound with a naturally cold sensation in mint. However, the effect of TRPM8 activation in inflammation and cardiac remodeling after myocardial infarction (MI) is not well defined. TRPM8 knockout (KO) mice (TRPM8-/-) and their wild-type littermates, aged 8 weeks, were randomly divided into sham and MI groups and were fed with chow or chow plus menthol. Dietary menthol significantly attenuated MI injury, evidenced by decreased survival rates and plasma cardiac troponion I levels, reduced infarct size and cardiomyocytes, declined collagen deposition, and rescued cardiac function and hemodynamics. However, these effects of menthol disappeared when mice were lacking TRPM8. Furthermore, feeding of menthol ameliorated elevated expression of inflammatory cytokines and chemokines, and aggravated inflammation infiltration in the MI mice but not in TRPM8-/- mice. In addition, menthol treatment increased the release of calcitonin gene-related peptide (CGRP), which were absent in TRPM8-/- mice. In conclusion, our results suggest that dietary menthol can protect against inflammation and cardiac remodeling after MI through activation of TRPM8.

Pharmacological inhibition of TRPM8-induced gene transcription

Transient receptor potential melastatin-8 (TRPM8) channels are activated by cold temperature, menthol and icilin, leading to cold sensation. TRPM8 activation is connected with various diseases, indicating that a specific pharmacological antagonist, allowing nongenetic channel suppression, would be a valuable tool for therapy and basic research. Here, we assessed the biological activity and specificity of various TRPM8 inhibitors following stimulation of TRPM8 channels with either icilin or menthol. Recently, we showed that icilin strikingly upregulates the transcriptional activity of AP-1. By measuring AP-1 activity, we assessed which compound interrupted the TRPM8-induced intracellular signaling cascade from the plasma membrane to the nucleus. We tested the specificity of various TRPM8 inhibitors by analyzing AP-1 activation following stimulation of TRPM3 and TRPV1 channels, L-type voltage-gated Ca2+ channels, and Gαq-coupled receptors, either in the presence or absence of a particular TRPM8 inhibitor. The results show that the TRPM8 inhibitors BCTC, RQ-00203078, TC-1 2014, 2-APB, and clotrimazole blocked TRPM8-mediated activation of AP-1. However, only the compound RQ-00203078 showed TRPM8-specificity, while the other compounds function as broad-spectrum Ca2+ channel inhibitors. In addition, we show that progesterone interfered with TRPM8-induced activation of AP-1, as previously shown for TRPM3 and TRPC6 channels. TRPM8-induced transcriptional activation of AP-1 was additionally blocked by the compound PD98059, indicating that extracellular signal-regulated protein kinase-1/2 is essential to couple TRPM8 stimulation with transcriptional activation of AP-1. Moreover, an influx of Ca2+-ions is essential to induce the intracellular signaling cascade leading to the activation of AP-1.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy Association With Low Cholesterol Levels: A Case Report in a Patient Taking PCSK9 Inhibitor

A 57-year-old woman with history of prediabetes and dyslipidemia treated with PCSK9 inhibitors due to statin intolerance presented to the clinic with complaints of bilateral thigh pain, weakness and numbness. During the physical exam, the patient exhibited stocking loss of vibratory and cold temperature sensation in both legs, absent ankle reflexes and tandem imbalance with normal cranial nerve functions. After all the clinical studies, the patient was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as an exclusion diagnosis. A link with medications (Praluent) was determined to be the most possible offending agent. With this case, we present a rare case of CIDP in the setting of low level of low-density lipoprotein cholesterol (LDL-C) due to PCSK9 inhibitors. This case opens the door to a new and unrecognized adverse effect of this type of medication. J Neurol Res. 2019;9(4-5):72-74 doi: https://doi.org/10.14740/jnr552

Evaluation of hot and cold sensation of hand in type 2 diabetic patients in age group of 40-80 years

Introduction: The aim of the study is to find out the effect of Type 2 diabetes (T2DM) on the hot and cold sensation of hand. Material and Method: Total100 subjects in the age group of 40-80 year, both male and female were included in this study. Subjects were divided into 2 groups. Group A: 50 subjects diagnosed type 2 diabetic mellitus. Group B: 50 normal healthy subjects investigated and diagnosed Non-diabetic mellitus. Before the start of the procedure, detailed neuro-musculoskeletal evaluation was done to meet inclusion and exclusion criteria and those who were ready to be part of the study, the written informed consent was obtained from them. Rolyan hot and cold discrimination kit was used to examine hot and cold sensation of both handsat pulp of index finger, little finger and dorsal web space. Result: There was loss of hot & cold sensation in 10% subjects of T2DM group at index and little finger bilaterally and all these subjects have the duration of diabetes >15yr. Conclusion: loss of sensation may lead to injuries of diabetic hands. Hand care should be thought to the patients to prevent injuries to the hand. Keywords: Type 2 diabetes, Hot and cold sensation, Diabetic hand.