Page last updated: 2024-10-21

menthol and Ache

menthol has been researched along with Ache in 43 studies

Menthol: A monoterpene cyclohexanol produced from mint oils.

Research Excerpts

ExcerptRelevanceReference
"We determined the effects of topically applied (i) isolated menthol cream, (ii) menthol and capsaicin co-application or (iii) placebo cream on exercise tolerance, thermal perception, pain, attentional focus and thermoregulation during exercise in the heat."9.69Topical application of isolated menthol and combined menthol-capsaicin creams: Exercise tolerance, thermal perception, pain, attentional focus and thermoregulation in the heat. ( Heffernan, SM; Jeffries, O; John, K; Page, J; Peel, J; Tallent, J; Waldron, M, 2023)
"Both health professionals and consumers use menthol-based topical analgesics extensively for the temporary relief of pain from musculoskeletal ailments or injury."9.51Menthol-Based Topical Analgesic Induces Similar Upper and Lower Body Pain Pressure Threshold Values: A Randomized Trial. ( Alizadeh, S; Behm, DG; Brosky, JA; Herat, N; Page, P; Power, GMJ, 2022)
"Burdens related to pain, smoking/nicotine dependence, and pain-smoking comorbidity disproportionately impact Black Americans, and menthol cigarette use is overrepresented among Black adults who smoke cigarettes."8.31Pain and Menthol Use Are Related to Greater Nicotine Dependence Among Black Adults Who Smoke Cigarettes at Wave 5 (2018-2019) of the Population Assessment of Tobacco and Health (PATH) Study. ( Deyo, AG; Ditre, JW; Heckman, BW; Powers, JM; Rubenstein, D; Terry, EL; Zale, EL, 2023)
"Nicotine has acute pain-relieving properties, and tobacco smokers often report using cigarettes to cope with pain."7.91Menthol cigarette use and pain reporting among African American adults seeking treatment for smoking cessation. ( Buckner, JD; Ditre, JW; Hughes, MT; Kosiba, JD; LaRowe, LR; Norton, PJ; Smits, JAJ; Zvolensky, MJ, 2019)
" It is therefore hypothesized in this paper that the esophageal infusion of the TRPM8 activator menthol evokes cold sensations from the esophagus and alleviates heartburn in humans."7.91The infusion of menthol into the esophagus evokes cold sensations in healthy subjects but induces heartburn in patients with gastroesophageal reflux disease (GERD). ( Banovcin, P; Duricek, M; Hyrdel, R; Kollarik, M; Liptak, P; Zatko, T, 2019)
"Topical high-concentration L-menthol is the only established human experimental pain model to study mechanisms underlying cold hyperalgesia."7.81Cold and L-menthol-induced sensitization in healthy volunteers--a cold hypersensitivity analogue to the heat/capsaicin model. ( Andersen, HH; Arendt-Nielsen, L; Gazerani, P; Nikbakht, A; Poulsen, JN; Uchida, Y, 2015)
"Topical capsaicin is reported to be an effective treatment for idiopathic intractable pruritus ani."7.72Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key. ( Anand, P, 2003)
"The effect of menthol and alcohol as its vehicle on thermal sensations, pain, experimental itch and irritation were studied in 18 subjects, using a computerized thermal sensory analyzer, laser Doppler flowmetry and an evaporimeter for transepidermal water loss (TEWL)."7.69Effect of topically applied menthol on thermal, pain and itch sensations and biophysical properties of the skin. ( Hui, XY; Maibach, H; Szolar, C; Yosipovitch, G, 1996)
"We determined the effects of topically applied (i) isolated menthol cream, (ii) menthol and capsaicin co-application or (iii) placebo cream on exercise tolerance, thermal perception, pain, attentional focus and thermoregulation during exercise in the heat."5.69Topical application of isolated menthol and combined menthol-capsaicin creams: Exercise tolerance, thermal perception, pain, attentional focus and thermoregulation in the heat. ( Heffernan, SM; Jeffries, O; John, K; Page, J; Peel, J; Tallent, J; Waldron, M, 2023)
"Both health professionals and consumers use menthol-based topical analgesics extensively for the temporary relief of pain from musculoskeletal ailments or injury."5.51Menthol-Based Topical Analgesic Induces Similar Upper and Lower Body Pain Pressure Threshold Values: A Randomized Trial. ( Alizadeh, S; Behm, DG; Brosky, JA; Herat, N; Page, P; Power, GMJ, 2022)
"Menthol inhibited phototoxicity-evoked APs and reduced pain behavior when applied topically to mice."5.48Menthol reduces phototoxicity pain in a mouse model of photodynamic therapy. ( Baptista-Hon, D; Bull, F; Dalgaty, F; Gallacher, M; Hales, TG; Ibbotson, SH; Wright, L, 2018)
" The search terms used were 'TRP channel AND plant compound', 'cough AND plant compound', 'cough AND TRP channels AND plant compound', 'cough AND P2X3 AND plant compound' and 'P2X3 AND plant compound' where plant compound represents menthol or camphor or eucalyptus or turpentine or thymol."5.41Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies. ( Morice, AH; Sadofsky, LR; Stinson, RJ, 2023)
"Menthol is a natural compound of plant origin known to produce cool sensation via the activation of the TRPM8 channel."5.38Menthol pain relief through cumulative inactivation of voltage-gated sodium channels. ( Delmas, P; Gabriac, M; Gaudioso, C; Hao, J; Martin-Eauclaire, MF, 2012)
"Cold hyperalgesia is 1 of the characteristic signs in neuropathic pain."5.37Topical high-concentration (40%) menthol-somatosensory profile of a human surrogate pain model. ( Baron, R; Binder, A; Klebe, O; Stengel, M; Wasner, G, 2011)
"Menthol has been used as a non-opioid pain reliever since ancient times."4.98The role and mechanism of action of menthol in topical analgesic products. ( LeQuang, JA; Pergolizzi, JV; Raffa, RB; Taylor, R, 2018)
"Burdens related to pain, smoking/nicotine dependence, and pain-smoking comorbidity disproportionately impact Black Americans, and menthol cigarette use is overrepresented among Black adults who smoke cigarettes."4.31Pain and Menthol Use Are Related to Greater Nicotine Dependence Among Black Adults Who Smoke Cigarettes at Wave 5 (2018-2019) of the Population Assessment of Tobacco and Health (PATH) Study. ( Deyo, AG; Ditre, JW; Heckman, BW; Powers, JM; Rubenstein, D; Terry, EL; Zale, EL, 2023)
"and purpose: Phenazopyridine (PAP) is an over-the-counter drug widely used to provide symptomatic relief of bladder pain in conditions such as cystitis or bladder pain syndrome (BPS)."4.31Inhibition of TRPM8 by the urinary tract analgesic drug phenazopyridine. ( Bazeli, B; Daniluk, J; Everaerts, W; Freitas, ACN; Janssens, A; Luyts, N; Mulier, M; Voets, T, 2023)
"Nicotine has acute pain-relieving properties, and tobacco smokers often report using cigarettes to cope with pain."3.91Menthol cigarette use and pain reporting among African American adults seeking treatment for smoking cessation. ( Buckner, JD; Ditre, JW; Hughes, MT; Kosiba, JD; LaRowe, LR; Norton, PJ; Smits, JAJ; Zvolensky, MJ, 2019)
" It is therefore hypothesized in this paper that the esophageal infusion of the TRPM8 activator menthol evokes cold sensations from the esophagus and alleviates heartburn in humans."3.91The infusion of menthol into the esophagus evokes cold sensations in healthy subjects but induces heartburn in patients with gastroesophageal reflux disease (GERD). ( Banovcin, P; Duricek, M; Hyrdel, R; Kollarik, M; Liptak, P; Zatko, T, 2019)
"Topical high-concentration L-menthol is the only established human experimental pain model to study mechanisms underlying cold hyperalgesia."3.81Cold and L-menthol-induced sensitization in healthy volunteers--a cold hypersensitivity analogue to the heat/capsaicin model. ( Andersen, HH; Arendt-Nielsen, L; Gazerani, P; Nikbakht, A; Poulsen, JN; Uchida, Y, 2015)
"Topical capsaicin is reported to be an effective treatment for idiopathic intractable pruritus ani."3.72Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key. ( Anand, P, 2003)
"The effect of menthol and alcohol as its vehicle on thermal sensations, pain, experimental itch and irritation were studied in 18 subjects, using a computerized thermal sensory analyzer, laser Doppler flowmetry and an evaporimeter for transepidermal water loss (TEWL)."3.69Effect of topically applied menthol on thermal, pain and itch sensations and biophysical properties of the skin. ( Hui, XY; Maibach, H; Szolar, C; Yosipovitch, G, 1996)
" Study I: A dose-response relationship (N = 20) between 0, 2, and 4 mg nicotine gum."2.82Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study. ( Arendt Nielsen, T; Arendt-Nielsen, L; Boudreau, SA; Nielsen, BP; Wang, K, 2016)
"Morphine was administered intramuscularly immediately prior to algogen administration."1.51Nociceptive-like behavior and analgesia in silver catfish (Rhamdia quelen). ( Baldisserotto, B; Barbosa, LB; Bianchini, AE; Ferrari, FT; Heinzmann, BM; Rodrigues, P, 2019)
"Menthol inhibited phototoxicity-evoked APs and reduced pain behavior when applied topically to mice."1.48Menthol reduces phototoxicity pain in a mouse model of photodynamic therapy. ( Baptista-Hon, D; Bull, F; Dalgaty, F; Gallacher, M; Hales, TG; Ibbotson, SH; Wright, L, 2018)
" AMG2850 is potent in vitro at rat TRPM8 (IC90 against icilin activation of 204 ± 28 nM), highly selective (>100-fold IC90 over TRPV1 and TRPA1 channels), and orally bioavailable (F po > 40 %)."1.42AMG2850, a potent and selective TRPM8 antagonist, is not effective in rat models of inflammatory mechanical hypersensitivity and neuropathic tactile allodynia. ( Davis, C; Gavva, NR; Kerstein, PC; Lehto, SG; Stucky, CL; Wang, J; Wang, W; Weyer, AD; Wild, KD; Youngblood, BD; Zhang, M, 2015)
"Menthol is a natural compound of plant origin known to produce cool sensation via the activation of the TRPM8 channel."1.38Menthol pain relief through cumulative inactivation of voltage-gated sodium channels. ( Delmas, P; Gabriac, M; Gaudioso, C; Hao, J; Martin-Eauclaire, MF, 2012)
"Cold hyperalgesia is 1 of the characteristic signs in neuropathic pain."1.37Topical high-concentration (40%) menthol-somatosensory profile of a human surrogate pain model. ( Baron, R; Binder, A; Klebe, O; Stengel, M; Wasner, G, 2011)
"Central neuropathic pain following lesions within the CNS, such as spinal cord injury, is one of the most excruciating types of chronic pain and one of the most difficult to treat."1.35Residual spinothalamic tract pathways predict development of central pain after spinal cord injury. ( Engel, S; Lee, BB; McLachlan, E; Wasner, G, 2008)

Research

Studies (43)

TimeframeStudies, this research(%)All Research%
pre-19904 (9.30)18.7374
1990's1 (2.33)18.2507
2000's11 (25.58)29.6817
2010's20 (46.51)24.3611
2020's7 (16.28)2.80

Authors

AuthorsStudies
Baraldi, PG1
Preti, D1
Materazzi, S1
Geppetti, P1
Behm, DG1
Herat, N1
Power, GMJ1
Brosky, JA1
Page, P1
Alizadeh, S1
Powers, JM1
Zale, EL1
Deyo, AG1
Rubenstein, D1
Terry, EL1
Heckman, BW1
Ditre, JW2
Luyts, N1
Daniluk, J1
Freitas, ACN1
Bazeli, B1
Janssens, A1
Mulier, M1
Everaerts, W1
Voets, T1
Stinson, RJ1
Morice, AH1
Sadofsky, LR1
Peel, J1
John, K1
Page, J1
Jeffries, O1
Heffernan, SM1
Tallent, J1
Waldron, M1
Halonen, L1
Pemmari, A1
Nummenmaa, E1
Hämäläinen, M1
Moilanen, T1
Vuolteenaho, K1
Moilanen, E1
Rodrigues, P1
Barbosa, LB1
Bianchini, AE1
Ferrari, FT1
Baldisserotto, B1
Heinzmann, BM1
Esancy, K1
Dhaka, A1
Lai, PM1
Collaku, A1
Reed, K1
Wright, L1
Baptista-Hon, D1
Bull, F1
Dalgaty, F1
Gallacher, M1
Ibbotson, SH1
Hales, TG1
Li, K1
Gao, S1
Tian, B1
Shi, Y1
Lv, Q1
Han, J1
Pergolizzi, JV1
Taylor, R1
LeQuang, JA1
Raffa, RB1
Kosiba, JD1
Hughes, MT1
LaRowe, LR1
Zvolensky, MJ1
Norton, PJ1
Smits, JAJ1
Buckner, JD1
Hondebrink, L1
Opstelten, W1
Banovcin, P1
Duricek, M1
Zatko, T1
Liptak, P1
Hyrdel, R1
Kollarik, M1
Wade, AG1
Crawford, GM1
Young, D1
Corson, S1
Brown, C1
Lehto, SG1
Weyer, AD1
Zhang, M1
Youngblood, BD1
Wang, J1
Wang, W1
Kerstein, PC1
Davis, C1
Wild, KD1
Stucky, CL1
Gavva, NR1
Andersen, HH1
Poulsen, JN1
Uchida, Y1
Nikbakht, A1
Arendt-Nielsen, L2
Gazerani, P1
Arendt Nielsen, T1
Nielsen, BP1
Wang, K1
Boudreau, SA1
Wasner, G3
Lee, BB1
Engel, S1
McLachlan, E1
Colvin, LA1
Johnson, PR1
Mitchell, R1
Fleetwood-Walker, SM1
Fallon, M1
Caspani, O1
Zurborg, S1
Labuz, D1
Heppenstall, PA1
Liu, K1
Samuel, M1
Ho, M1
Harrison, RK1
Paslay, JW1
Klein, AH1
Sawyer, CM1
Carstens, MI1
Tsagareli, MG1
Tsiklauri, N1
Carstens, E1
Binder, A2
Stengel, M1
Klebe, O1
Baron, R2
Roberts, K1
Shenoy, R1
Anand, P2
Gaudioso, C1
Hao, J1
Martin-Eauclaire, MF1
Gabriac, M1
Delmas, P1
Renner, B1
Schreiber, K1
Averbeck, B1
Rucker, F1
Laubender, RP1
Carr, RW1
KLEINMAN, H1
COONEY, MK1
NELSON, CB1
OWEN, RR1
BOYD, L1
SWANDA, G1
Schattschneider, J1
Kraemer, WJ1
Ratamess, NA1
Maresh, CM1
Anderson, JA1
Volek, JS1
Tiberio, DP1
Joyce, ME1
Messinger, BN1
French, DN1
Sharman, MJ1
Rubin, MR1
Gómez, AL1
Silvestre, R1
Hesslink, RL1
Namer, B2
Seifert, F1
Handwerker, HO1
Maihöfner, C1
Liu, Y1
Ye, X1
Feng, X1
Zhou, G1
Rong, Z1
Fang, C1
Chen, H1
Linte, RM1
Ciobanu, C1
Reid, G1
Babes, A1
Kleggetveit, IP1
Handwerker, H1
Schmelz, M1
Jorum, E1
Yosipovitch, G1
Szolar, C1
Hui, XY1
Maibach, H1
Acosta, MC1
Belmonte, C1
Gallar, J1
Kobal, G1
Raab, W1
Lotz, H1
White, JR1

Clinical Trials (3)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Clinical Study to Assess the Efficacy and Onset of Pain Relief of Topical MFC51123 Diclofenac-Menthol Gel Versus Controls in Ankle Sprain[NCT02100670]Phase 3385 participants (Actual)Interventional2013-11-01Completed
Comparison of Topical 1% Diclofenac and Topical 2.5% Hydrocortisone for TMJ Arthralgia[NCT05816226]Phase 390 participants (Anticipated)Interventional2023-06-01Recruiting
High-concentration L-menthol as a Counter-irritant to TRPA1-induced Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde[NCT02653703]14 participants (Actual)Interventional2014-10-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Area Under the Curve From Day 1 to Day 3 (AUC1-3 Days) of Pain Intensity(PI) on Movement for Diclofenac/Methanol Gel and Placebo Gel

AUC of PI on movement was measured by a numerical rating scale (NRS) during the 48 hour time interval from Day 1 to 3. AUC1-3 day was calculated based on trapezoidal method. Pain intensity was measured in NRS scale from 0 (no pain) to 10 (extreme pain). Participants assessed the severity of ankle pain using the NRS scale at baseline (prior to treatment) and at 10, 30 minutes and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing. (NCT02100670)
Timeframe: up to 72 hours

InterventionNRS Score (0 - 10 scale) * hrs (Mean)
1% Diclofenac Sodium Plus (+) 3% Menthol276.97
Placebo282.88

AUC1-3 Days of PI on Movement for Diclofenac Sodium + Methanol, Diclofenac, Methanol and Placebo

AUC of PI on movement was measured by a numerical rating scale (NRS) during the 48 hour time interval from Day 1 to 3. AUC1-3 day was calculated based on trapezoidal method. Pain intensity was measured in NRS scale from 0 (no pain) to 10 (extreme pain). Participants assessed the severity of ankle pain using the NRS scale at baseline (prior to treatment) and at 10, 30 minutes and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing. (NCT02100670)
Timeframe: up to 72 hours

InterventionNRS Score (0 - 10 scale) * hrs (Mean)
1% Diclofenac Sodium+3% Menthol276.97
1% Diclofenac Sodium261.11
3% Menthol272.65
Placebo282.88

Time of Onset of Cooling Sensation (TOCS)

"Time of onset of cooling sensation measured by time when subjects reported to have a 'cooling effect as an enhancement of pain relief'. To assess this endpoint, participants were asked at 10, 30 minutes and at 1, 4, 6 hours post first dose Do you feel a cooling sensation at the injured ankle from the study gel?" (NCT02100670)
Timeframe: up to 6 hours

InterventionHours (Median)
1% Diclofenac Sodium+3% Menthol0.17
1% Diclofenac Sodium0.17
3% Menthol0.17
Placebo0.17

Time of Onset of Meaningful Pain Relief (TOMR)

"TOMR was measured by time when participants reported PRS ≥ 2, i.e. some or meaningful pain relief" (NCT02100670)
Timeframe: up to 10 days (end of study)

InterventionHours (Median)
1% Diclofenac Sodium+3% Menthol92.50
1% Diclofenac Sodium76.83
3% Menthol72.00
Placebo93.50

Time of Onset of Pain Relief (TOPR)

"TOPR was measured by time when participants reported PRS ≥ 1, i.e. a little or perceptible pain relief'." (NCT02100670)
Timeframe: Baseline to 10 days (end of study)

InterventionHours (Median)
1% Diclofenac Sodium+3% Menthol1.03
1% Diclofenac Sodium4.00
3% Menthol1.00
Placebo4.00

Time to Complete Recovery

Time to complete recovery measured as the day with complete relief of ankle pain (Participant-rated NRS scores were 0 for pain intensity at rest and pain) and swelling (Participants did not have any apparent swelling nor experience any pain or limitation of movement of the injured ankle as determined by the Principal Investigator or designee during the course of an ankle exam). (NCT02100670)
Timeframe: up to 240 hours

InterventionHours (Median)
1% Diclofenac Sodium+3% Menthol240.00
1% Diclofenac Sodium240.00
3% Menthol240.00
Placebo240.00

Ankle Swelling

"Ankle swelling measured by figure of eight method of injured ankle." (NCT02100670)
Timeframe: Day 1 (baseline), 3, and 7

,,,
InterventionMillimeters (Mean)
At Day 1At Day 3At Day 7
1% Diclofenac Sodium573.6566.9558.8
1% Diclofenac Sodium+3% Menthol573.9566.2558.3
3% Menthol577.1567.0558.4
Placebo576.1565.4557.0

Pain Intensity Difference (PID) on Movement

"PID on movement, calculated as PI at a given time 't' (after walking 5 steps on a flat surface) subtracted by the PI at baseline.~Participants assessed the severity of ankle pain (PI) using the NRS scale from 0 (no pain) to 10 (extreme pain). PI was measured at baseline (prior to treatment) and at 10, 30 minutes (min.) and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing." (NCT02100670)
Timeframe: Baseline to 10 days

,,,
Interventionscore on scale (Mean)
PI at Baseline (n=117, 112, 77, 75)PID at 10 min. (n=117, 112, 77, 75)PID at 30 min. (n=117, 112, 77, 75)PID at 1 hour (n=117, 112, 77, 75)PID at 4 hour (n=117, 112, 77, 75)PID at 6 hour (n=117, 112, 77, 75)PID at 12 hour (n= 117, 112, 77, 75)PID at 18 hour (n=117, 112, 77, 75)PID at 24 hour (n=117, 112, 77, 75)PID at 36 hour (n=117, 112, 77, 75)PID at 48 hour (n=117, 112, 77, 75)PID at 60 hour (n=117, 112, 77, 75)PID at 72 hour (n=117, 112, 77, 75)PID at 84 hour (n=113, 107, 75, 75)PID at 96 hour (n=112, 107, 75, 74)PID at 108 hour (n=112, 107, 75, 74)PID at 120 hour (n=111, 107, 74, 74)PID at 132 hour (n=110, 107, 74, 74)PID at 144 hour (n=110, 107, 74, 74)PID at 156 hour (n=109, 107, 74, 74)PID at 168 hour (n=105, 104, 73, 74)PID at 180 hour (n=105, 104, 73, 72)PID at 192 hour (n=101, 102, 71, 72)PID at 204 hour (n=101, 100, 71, 72)PID at 216 hour (n=95, 100, 69, 72)PID at 228 hour (n=95, 100, 69, 72)PID at 240 hour (n=32, 43, 22, 42)
1% Diclofenac Sodium7.40.190.360.500.480.670.991.321.581.652.012.262.422.682.783.013.173.533.784.054.114.454.594.945.215.625.44
1% Diclofenac Sodium+3% Menthol7.80.230.440.560.710.790.841.191.621.591.912.412.552.843.103.343.383.703.764.174.264.584.555.175.285.715.56
3% Menthol7.80.290.490.640.790.911.171.441.751.552.042.562.553.083.033.483.353.723.683.953.904.374.214.874.875.285.41
Placebo7.70.320.550.640.690.870.951.161.531.321.922.052.282.682.783.183.143.473.593.883.954.084.224.564.785.015.60

Pain Relief Score (PRS)

Pain relief was measured at each time point using a 5-point Pain Relief Scale ranging from 0-4 while at rest (Where: 0- No pain relief; 1- A little or perceptible pain relief; 2- Meaningful pain relief; 3- A lot of relief; 4- Complete relief). Participants assessed the degree of ankle pain relief using the PRS scores at 10, 30 minutes and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after the first day of treatment. (NCT02100670)
Timeframe: Day 1 to Day 7

,,,
Interventionscore on a scale (Mean)
At 10 min. (n= 117, 111, 77, 74)At 30 min. (n=117, 111, 77, 75)At 1 hour (n=116, 112, 77, 75)At 4 hour (n= 115, 110, 74, 71)At 6 hour (n= 109, 105, 70, 69)At 12 hour (n= 77, 89, 53, 58)At 18 hour (n= 76, 78, 53, 57)At 24 hour (n= 111, 105, 72, 72)At 36 hour (n= 116, 112, 77, 74)At 48 hour (n= 116, 112, 77, 75)At 60 hour (n=115, 111, 77, 75)At 72 hour (n= 114, 109, 75, 74)At 84 hour (n= 113, 106, 75, 75)At 96 hour (n= 112, 106, 75, 74)At 108 hour (n= 111, 105, 75, 74)At 120 hour (n= 111, 107, 74, 72)At 132 hour (n= 110, 107, 73, 74)At 144 hour (n= 110, 107, 74, 73)At 156 hour (n= 109, 106, 74, 74)At 168 hour (n= 105, 103, 73, 73)
1% Diclofenac Sodium0.290.360.460.450.540.720.730.740.840.841.001.061.001.031.131.141.241.211.301.31
1% Diclofenac Sodium+3% Menthol0.330.440.480.470.500.600.710.790.840.901.070.931.071.091.181.111.341.211.411.41
3% Menthol0.320.490.570.510.630.740.830.900.880.991.161.161.251.011.281.241.341.301.471.34
Placebo0.360.440.400.490.450.620.700.810.780.990.960.971.111.091.151.101.301.271.321.40

Patient's Global Assessment in Response to Treatment (PGART)

PGART was measured at the end of study in a scale from 0-4 (Where: 0- Poor; 1- Fair; 2- Good; 3- Very Good; 4- Excellent) (NCT02100670)
Timeframe: up to Day 10

,,,
InterventionParticipants (Number)
Poor=0Fair=1Good=2Very Good=3Excellent=4
1% Diclofenac Sodium132046266
1% Diclofenac Sodium+3% Menthol32444359
3% Menthol61226265
Placebo91427214

PID at Rest

"PID at rest was calculated as PI at a given time point't' (at rest) subtracted by the PI at baseline. Participants assessed the severity of ankle pain (PI) using the NRS scale from 0 (no pain) to 10 (extreme pain).~PI was measured at baseline (prior to treatment) and at 10, 30 minutes and 1, 4, 6, 12, 18 and 24 hours after the first dose of treatment and twice daily after dosing." (NCT02100670)
Timeframe: Baseline to 10 days

,,,
Interventionscore on a scale (Mean)
PI at Baseline (n=117, 112, 77, 75)PID at 10 min. (n=117, 112, 77, 75)PID at 30 min. (n=117, 112, 77, 75)PID at 1 hour (n=117, 112, 77, 75)PID at 4 hour (n=117, 112, 77, 75)PID at 6 hour (n= 117, 112, 77, 75)PID at 12 hour (n= 117, 112, 77, 75)PID at 18 hour (n= 117, 112, 77, 75)PID at 24 hour (n= 117, 112, 77, 75)PID at 36 hour (n= 117, 112, 77, 75)PID at 48 hour (n=117, 112, 77, 75)PID at 60 hour (n= 117, 112, 77, 75)PID at 72 hour (n= 117, 112, 77, 75)PID at 84 hour (n= 113, 107, 75, 75)PID at 96 hour (n= 112, 107, 75, 74)PID at 108 hour (n=112, 107, 75, 74)PID at 120 hour (n= 111, 107, 74, 74)PID at 132 hour (n= 110, 107, 74, 74)PID at 144 hour (n= 110, 107, 74, 74)PID at 156 hour (n= 109, 107, 74, 74)PID at 168 hour (n= 105, 104, 73, 74)PID at 180 hour (n= 105, 104, 73, 72)PID at 192 hour (n= 101, 102, 71, 72)PID at 204 hour (n= 101, 100, 71, 72)PID at 216 hour (n= 95, 100, 69, 72)PID at 228 hour (n= 95, 100, 69, 72)PID at 240 hour (n= 32, 43, 22, 42)
1% Diclofenac Sodium7.40.430.450.620.530.620.861.141.391.321.531.831.912.192.172.432.482.782.773.113.153.383.303.613.874.024.23
1% Diclofenac Sodium+3% Menthol7.80.340.560.640.620.680.761.031.321.201.431.911.912.112.262.462.592.762.773.063.083.373.383.673.774.093.94
3% Menthol7.80.170.320.480.660.750.901.101.471.221.511.881.862.192.232.482.302.682.592.772.752.952.903.373.223.643.36
Placebo7.70.250.440.410.430.530.680.851.131.091.451.641.762.032.002.272.092.492.492.652.642.883.003.213.263.533.67

Skin Temperature

Skin temperature was measured by thermal imaging. (NCT02100670)
Timeframe: At 10, 30, 60 minutes, 4 and 6 hours

,,,
Interventiondegree celsius (°C) (Mean)
At 10 min.At 30 min.At 60 min.At 240 min.At 360 min.
1% Diclofenac Sodium29.3129.8130.7431.2631.53
1% Diclofenac Sodium+3% Menthol27.6928.2628.6430.5231.02
3% Menthol29.9230.5030.2231.1531.27
Placebo30.9331.4731.7831.5732.07

Sum of Pain Intensity Difference (SPID)

SPID was calculated as the time weighted sum of pain intensity differences (PID) from 0 to 7 Days. PID was calculated as PI at a given time point 't' subtracted by the PI at baseline. PI was measured on NRS scale from 0 (no pain) to 10 (extreme pain). The possible range of SPID for 0-6 hours was from -60 to 60, for 0-12 hours was from -120 to 120, for 0-1 day was from -240 to 240, for 0-3 days was from -720 to 720, for 0-7 days was from -1680 to 1680. A higher value of SPID indicates greater pain relief. (NCT02100670)
Timeframe: Baseline to Day 7

,,,
Interventionscore on a scale (Mean)
At 0-6 hoursAt 0-12 hoursAt 0-1 daysAt 1 to 3 daysAt 0 to 7 days
1% Diclofenac Sodium3.199.1326.54100.07452.44
1% Diclofenac Sodium+3% Menthol4.169.1926.01101.54451.12
3% Menthol4.7211.7430.91104.26464.96
Placebo4.3710.0526.2190.88438.45

Total Pain Relief (TOTPAR)

TOTPAR was calculated as sum of the products of PRS with time interval from one time point to the other. PRS was measured at each time point on a scale: 0= No pain relief, 1= A little or perceptible pain relief, 2= Meaningful pain relief, 3= A lot of relief, 4= Complete relief. The possible range of TOTPAR for 0-6 hours was from 0 to 24, for 0-12 hours was from 0 to 48, for 0-24 hours was from 0 to 96, for 0-72 hours was from 0 to 288, for 24-72 hours was from 0 to 192 and for 0-168 hours was from 0 to 672. (NCT02100670)
Timeframe: Baseline to 168 hours

,,,
InterventionPRS Score (0 - 4 scale) (Mean)
0-6 hours0-12 hours0- 24 hours0-72 hours24-72 hours0-168 hours
1% Diclofenac Sodium2.646.8116.1461.2445.11170.73
1% Diclofenac Sodium+3% Menthol2.816.8616.0460.1444.10172.97
3% Menthol3.278.0218.8566.6947.84184.17
Placebo2.756.3515.7158.7543.04174.00

Reviews

3 reviews available for menthol and Ache

ArticleYear
Transient receptor potential ankyrin 1 (TRPA1) channel as emerging target for novel analgesics and anti-inflammatory agents.
    Journal of medicinal chemistry, 2010, Jul-22, Volume: 53, Issue:14

    Topics: Analgesics; Animals; Anti-Inflammatory Agents; Asthma; Humans; Ion Channel Gating; Neurons; Pain; Pe

2010
Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies.
    Respiratory research, 2023, Feb-08, Volume: 24, Issue:1

    Topics: Analgesics; Camphor; Cough; Humans; Menthol; Pain; Transient Receptor Potential Channels; TRPA1 Cati

2023
The role and mechanism of action of menthol in topical analgesic products.
    Journal of clinical pharmacy and therapeutics, 2018, Volume: 43, Issue:3

    Topics: Administration, Cutaneous; Analgesics; Humans; Menthol; Pain; TRPM Cation Channels

2018

Trials

13 trials available for menthol and Ache

ArticleYear
Menthol-Based Topical Analgesic Induces Similar Upper and Lower Body Pain Pressure Threshold Values: A Randomized Trial.
    Journal of sport rehabilitation, 2022, 01-01, Volume: 31, Issue:1

    Topics: Achilles Tendon; Analgesics; Female; Humans; Male; Menthol; Pain; Pain Threshold

2022
Topical application of isolated menthol and combined menthol-capsaicin creams: Exercise tolerance, thermal perception, pain, attentional focus and thermoregulation in the heat.
    European journal of sport science, 2023, Volume: 23, Issue:10

    Topics: Adult; Body Temperature Regulation; Capsaicin; Cross-Over Studies; Exercise Tolerance; Female; Hot T

2023
Efficacy and safety of topical diclofenac/menthol gel for ankle sprain: A randomized, double-blind, placebo- and active-controlled trial.
    The Journal of international medical research, 2017, Volume: 45, Issue:2

    Topics: Administration, Cutaneous; Adolescent; Adult; Ankle; Ankle Injuries; Anti-Inflammatory Agents, Non-S

2017
Comparison of diclofenac gel, ibuprofen gel, and ibuprofen gel with levomenthol for the topical treatment of pain associated with musculoskeletal injuries.
    The Journal of international medical research, 2019, Volume: 47, Issue:9

    Topics: Administration, Topical; Adolescent; Adult; Aged; Diclofenac; Female; Gels; Humans; Ibuprofen; Male;

2019
Psychophysical and Vasomotor Responses of the Oral Tissues: A Nicotine Dose-Response and Menthol Interaction Study.
    Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2016, Volume: 18, Issue:5

    Topics: Adult; Blood Pressure; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Dr

2016
Olfactory and trigeminal interaction of menthol and nicotine in humans.
    Experimental brain research, 2012, Volume: 219, Issue:1

    Topics: Adult; Analysis of Variance; Cross-Sectional Studies; Dose-Response Relationship, Drug; Double-Blind

2012
Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors.
    Brain : a journal of neurology, 2004, Volume: 127, Issue:Pt 5

    Topics: Administration, Topical; Adult; Aged; Antipruritics; Cold Temperature; Double-Blind Method; Female;

2004
A cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in individuals with arthritis.
    Journal of strength and conditioning research, 2005, Volume: 19, Issue:2

    Topics: Activities of Daily Living; Administration, Topical; Aged; Arthritis; Drug Combinations; Elbow; Fatt

2005
TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol.
    Neuroreport, 2005, Jun-21, Volume: 16, Issue:9

    Topics: Acrolein; Adult; Axons; Cross-Over Studies; Double-Blind Method; Female; Humans; Hyperalgesia; Ion C

2005
Menthol facilitates the skin analgesic effect of tetracaine gel.
    International journal of pharmaceutics, 2005, Nov-23, Volume: 305, Issue:1-2

    Topics: Adult; Anesthetics, Local; Animals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Comb

2005
Role of TRPM8 and TRPA1 for cold allodynia in patients with cold injury.
    Pain, 2008, Sep-30, Volume: 139, Issue:1

    Topics: Acrolein; Adult; Afferent Pathways; Calcium Channels; Cold Temperature; Cross-Over Studies; Double-B

2008
The effects of analgesics on pain-related somatosensory evoked potentials.
    Agents and actions. Supplements, 1986, Volume: 19

    Topics: Analgesics; Carbon Dioxide; Dental Pulp; Dipyrone; Electric Stimulation; Evoked Potentials; Humans;

1986
Effects of a counterirritant on perceived pain and hand movement in patients with arthritis.
    Physical therapy, 1973, Volume: 53, Issue:9

    Topics: Adult; Aged; Arthritis, Rheumatoid; Audiometry; Female; Finger Joint; Hand; Humans; Irritants; Male;

1973

Other Studies

27 other studies available for menthol and Ache

ArticleYear
Pain and Menthol Use Are Related to Greater Nicotine Dependence Among Black Adults Who Smoke Cigarettes at Wave 5 (2018-2019) of the Population Assessment of Tobacco and Health (PATH) Study.
    Journal of racial and ethnic health disparities, 2023, Volume: 10, Issue:5

    Topics: Adult; Cigarette Smoking; Humans; Menthol; Nicotiana; Pain; Tobacco Products; Tobacco Use Disorder

2023
Inhibition of TRPM8 by the urinary tract analgesic drug phenazopyridine.
    European journal of pharmacology, 2023, Mar-05, Volume: 942

    Topics: Animals; Calcium; Cricetinae; Cricetulus; Fura-2; Ganglia, Spinal; HEK293 Cells; Humans; Menthol; Mi

2023
Human Osteoarthritic Chondrocytes Express Nineteen Different TRP-Genes-TRPA1 and TRPM8 as Potential Drug Targets.
    International journal of molecular sciences, 2023, Jun-13, Volume: 24, Issue:12

    Topics: Chondrocytes; Dexamethasone; Humans; Membrane Proteins; Menthol; Pain; Protein Serine-Threonine Kina

2023
Nociceptive-like behavior and analgesia in silver catfish (Rhamdia quelen).
    Physiology & behavior, 2019, 10-15, Volume: 210

    Topics: Acetic Acid; Analgesia; Analgesics, Opioid; Animals; Catfishes; Disease Models, Animal; Injections;

2019
Unveiling new mechanisms for cold sensitization.
    Pain, 2021, 02-01, Volume: 162, Issue:2

    Topics: Ankyrins; Humans; Menthol; Neurogenic Inflammation; Nociception; Pain; Receptors, Nerve Growth Facto

2021
Menthol reduces phototoxicity pain in a mouse model of photodynamic therapy.
    Pain, 2018, Volume: 159, Issue:2

    Topics: Acrylamides; Animals; Animals, Newborn; Antipruritics; Bridged Bicyclo Compounds, Heterocyclic; Derm

2018
Formulation Optimization and In-vitro and In-vivo Evaluation of Lornoxicam Ethosomal Gels with Penetration Enhancers.
    Current drug delivery, 2018, Volume: 15, Issue:3

    Topics: Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cholesterol; Drug Compoun

2018
Menthol cigarette use and pain reporting among African American adults seeking treatment for smoking cessation.
    Experimental and clinical psychopharmacology, 2019, Volume: 27, Issue:3

    Topics: Adult; Black or African American; Cigarette Smoking; Female; Humans; Male; Menthol; Middle Aged; Mot

2019
A woman with an itchy hyperpigmentation on her back.
    BMJ (Clinical research ed.), 2019, Apr-11, Volume: 365

    Topics: Aged; Back; Female; Histamine Antagonists; Humans; Hyperpigmentation; Menthol; Pain; Pruritus; Skin;

2019
The infusion of menthol into the esophagus evokes cold sensations in healthy subjects but induces heartburn in patients with gastroesophageal reflux disease (GERD).
    Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus, 2019, Dec-30, Volume: 32, Issue:11

    Topics: Adult; Afferent Pathways; Aged; Esophagus; Female; Gastroesophageal Reflux; Healthy Volunteers; Hear

2019
AMG2850, a potent and selective TRPM8 antagonist, is not effective in rat models of inflammatory mechanical hypersensitivity and neuropathic tactile allodynia.
    Naunyn-Schmiedeberg's archives of pharmacology, 2015, Volume: 388, Issue:4

    Topics: Action Potentials; Animals; Behavior, Animal; Blood Pressure; Brain; Calcium; CHO Cells; Cold Temper

2015
Cold and L-menthol-induced sensitization in healthy volunteers--a cold hypersensitivity analogue to the heat/capsaicin model.
    Pain, 2015, Volume: 156, Issue:5

    Topics: Administration, Topical; Adult; Capsaicin; Cold Temperature; Female; Hand; Hot Temperature; Humans;

2015
Residual spinothalamic tract pathways predict development of central pain after spinal cord injury.
    Brain : a journal of neurology, 2008, Volume: 131, Issue:Pt 9

    Topics: Adult; Capsaicin; Cold Temperature; Female; Histamine; Hot Temperature; Humans; Male; Menthol; Middl

2008
From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008, Sep-20, Volume: 26, Issue:27

    Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Boronic Acids; Borte

2008
The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain.
    PloS one, 2009, Oct-08, Volume: 4, Issue:10

    Topics: Animals; Ankyrins; Calcium; Calcium Channels; Cold Temperature; Ganglia, Spinal; Male; Menthol; Mice

2009
NPPB structure-specifically activates TRPA1 channels.
    Biochemical pharmacology, 2010, Jul-01, Volume: 80, Issue:1

    Topics: Calcium Channels; Cell Line; Humans; Isothiocyanates; Kidney; Menthol; Mutagenesis; Nerve Tissue Pro

2010
Topical application of L-menthol induces heat analgesia, mechanical allodynia, and a biphasic effect on cold sensitivity in rats.
    Behavioural brain research, 2010, Oct-15, Volume: 212, Issue:2

    Topics: Administration, Topical; Aging; Animals; Antipruritics; Cold Temperature; Dose-Response Relationship

2010
Topical high-concentration (40%) menthol-somatosensory profile of a human surrogate pain model.
    The journal of pain, 2011, Volume: 12, Issue:7

    Topics: Administration, Topical; Adult; Antipruritics; Dose-Response Relationship, Drug; Hand; Humans; Hyper

2011
A novel human volunteer pain model using contact heat evoked potentials (CHEP) following topical skin application of transient receptor potential agonists capsaicin, menthol and cinnamaldehyde.
    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2011, Volume: 18, Issue:7

    Topics: Acrolein; Adult; Capsaicin; Electroencephalography; Evoked Potentials; Female; Hot Temperature; Huma

2011
Menthol pain relief through cumulative inactivation of voltage-gated sodium channels.
    Pain, 2012, Volume: 153, Issue:2

    Topics: Analgesics; Animals; Cell Line, Tumor; Hybrid Cells; Male; Menthol; Mice; Mice, Inbred C57BL; NAV1.8

2012
Thermal grill-evoked sensations of heat correlate with cold pain threshold and are enhanced by menthol and cinnamaldehyde.
    European journal of pain (London, England), 2013, Volume: 17, Issue:5

    Topics: Acrolein; Adult; Cold Temperature; Female; Hot Temperature; Humans; Male; Menthol; Nociceptors; Pain

2013
Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key.
    Gut, 2003, Volume: 52, Issue:9

    Topics: Administration, Topical; Animals; Antipruritics; Capsaicin; Humans; Menthol; Pain; Pruritus Ani; Rec

2003
TRACTION DEVICE EASES PAIN OF TRAVEL.
    JAMA, 1964, Jan-11, Volume: 187

    Topics: Humans; Menthol; Pain; Traction; Travel

1964
Desensitization of cold- and menthol-sensitive rat dorsal root ganglion neurones by inflammatory mediators.
    Experimental brain research, 2007, Volume: 178, Issue:1

    Topics: Analgesia; Animals; Ankyrins; Antipruritics; Calcium Channels; Cells, Cultured; Cold Temperature; Cy

2007
Effect of topically applied menthol on thermal, pain and itch sensations and biophysical properties of the skin.
    Archives of dermatological research, 1996, Volume: 288, Issue:5-6

    Topics: Administration, Topical; Adult; Biophysical Phenomena; Biophysics; Female; Histamine; Hot Temperatur

1996
Sensory experiences in humans and single-unit activity in cats evoked by polymodal stimulation of the cornea.
    The Journal of physiology, 2001, Jul-15, Volume: 534, Issue:Pt. 2

    Topics: Acids; Adult; Animals; Antipruritics; Carbon Dioxide; Cats; Cold Temperature; Cornea; Female; Hot Te

2001
[Therapeutic experiences with Dolo-Menthoneuringel].
    Zeitschrift fur Allgemeinmedizin, 1973, Jun-20, Volume: 49, Issue:17

    Topics: Back Pain; Drug Combinations; Evaluation Studies as Topic; Gels; Heparin; Humans; Menthol; Neuralgia

1973