The consequences of long-term topical capsaicin application in the rat

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p < 0.01). CBF returned to preischemic levels ∼45 min after reperfusion and was reduced to ∼65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p < 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p < 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 n M; 50 μl) to the middle or posterior temporal branch of the MCA 10–14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (Paco2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to reduce severe cortical hyperemia.

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Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.8.2974 ◽

1997 ◽

Vol 15 (8) ◽

pp. 2974-2980 ◽

Cited By ~ 110

Author(s):

N Ellison ◽

C L Loprinzi ◽

J Kugler ◽

A K Hatfield ◽

A Miser ◽

...

Keyword(s):

Neuropathic Pain ◽

Controlled Trial ◽

Phase Iii ◽

Painful Site ◽

Average Pain ◽

Skin Redness ◽

Topical Capsaicin ◽

Chili Peppers ◽

Placebo Cream

PURPOSE A minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial. PATIENTS AND METHODS Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires. RESULTS During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P < .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001). CONCLUSION A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference.

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Priming of central- and peripheral mechanisms with heat and cutaneous capsaicin facilitates secondary hyperalgesia to high frequency electrical stimulation

Journal of Neurophysiology ◽

10.1152/jn.00154.2021 ◽

2022 ◽

Author(s):

Rosa Hugosdottir ◽

Mindy Kasting ◽

Carsten Dahl Mørch ◽

Ole Kæseler Andersen ◽

Lars Arendt-Nielsen

Keyword(s):

High Frequency ◽

Blood Perfusion ◽

Control Area ◽

High Frequency Stimulation ◽

Secondary Hyperalgesia ◽

Capsaicin Application ◽

Heat Pain Threshold ◽

Frequency Stimulation ◽

Topical Capsaicin ◽

Chronic Pain Conditions

Heat/capsaicin sensitization and electrical high frequency stimulation (HFS) are well known model of secondary hyperalgesia, a phenomenon related to chronic pain conditions. This study investigated whether priming with heat/capsaicin would facilitate hyperalgesia to HFS in healthy subjects. Heat/capsaicin priming consisted of a 45 °C heat stimulation for 5 min followed by a topical capsaicin patch (4x4 cm) for 30 minutes on the volar forearm of 20 subjects. HFS (100 Hz, 5 times 1s, minimum 1.5 mA) was subsequently delivered through a transcutaneous pin electrode approximately 1.5 cm proximal to the heat/capsaicin application. Two sessions were applied in a crossover design; traditional HFS (HFS) and heat/capsaicin sensitization followed by HFS (HFS+HEAT/CAPS). Heat pain threshold (HPT), mechanical pain sensitivity (MPS) and superficial blood perfusion were assessed at baseline, after capsaicin removal, and up to 40 min after HFS. MPS was assessed with pinprick stimulation (128 mN and 256 mN) in the area adjacent to both HFS and heat/capsaicin, distal but adjacent to heat/capsaicin and in a distal control area. HPT was assessed in the area of heat/capsaicin. Higher sensitivity to 128 mN pinprick stimulation (difference from baseline and control area) was observed in the HFS+HEAT/CAPS session than in the HFS session 20 and 30 minutes after HFS. Furthermore, sensitivity was increased after HFS+HEAT/CAPS compared to after heat/capsaicin in the area adjacent to both paradigms, but not in the area distal to heat/capsaicin. Results indicate that heat/capsaicin causes priming of the central- and peripheral nervous system, which facilitates secondary mechanical hyperalgesia to HFS.

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Management of Cannabinoid Hyperemesis Syndrome: Focus on Capsaicin

Journal of Pharmacy Practice ◽

10.1177/0897190020934289 ◽

2020 ◽

pp. 089719002093428

Author(s):

Janice L. Stumpf ◽

Lauren D. Williams

Keyword(s):

Abdominal Pain ◽

Clinical Presentation ◽

Marijuana Use ◽

Hot Water ◽

Severe Nausea ◽

Trpv1 Receptors ◽

Cannabinoid Hyperemesis Syndrome ◽

Topical Capsaicin

Cannabinoid hyperemesis syndrome is a condition characterized by cyclic severe nausea, vomiting, and abdominal pain associated with frequent, long-term marijuana use. The condition resolves with cessation of cannabis but may be temporarily relieved by bathing in hot water. Topical capsaicin cream may also alleviate symptoms, perhaps through antiemetic effects produced by activation of TRPV1 receptors, similar to that of hot water bathing. This review summarizes the epidemiology, clinical presentation, diagnosis, pathophysiology, and management of cannabinoid hyperemesis syndrome, focusing on treatment with topical capsaicin.

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A comparison of morphological effects on the rabbit nasal and sinus mucosa after surgical denervation and topical capsaicin application

European Archives of Oto-Rhino-Laryngology ◽

10.1007/bf00171129 ◽

1996 ◽

Vol 253 (4-5) ◽

Cited By ~ 11

Author(s):

T. Norlander ◽

W.E. Bolger ◽

P. Stierna ◽

R. Uddman ◽

B. Carls��

Keyword(s):

Capsaicin Application ◽

Topical Capsaicin ◽

Sinus Mucosa

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Effect of Topical Analgesia on Desensitization Following 8% Topical Capsaicin Application

Journal of Pain ◽

10.1016/j.jpain.2021.01.005 ◽

2021 ◽

Author(s):

Janne D. Christensen ◽

Silvia Lo Vecchio ◽

Hjalte H. Andersen ◽

Jesper Elberling ◽

Lars Arendt-Nielsen

Keyword(s):

Capsaicin Application ◽

Topical Capsaicin ◽

Topical Analgesia

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Topical Capsaicin for Treating Cannabinoid Hyperemesis Syndrome

Case Reports in Gastrointestinal Medicine ◽

10.1155/2020/8868385 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Ansar Aziz ◽

Tayyab Waheed ◽

Olubunmi Oladunjoye ◽

Adeolu Oladunjoye ◽

Midhat Hanif ◽

...

Keyword(s):

Epigastric Pain ◽

Symptomatic Improvement ◽

Nausea And Vomiting ◽

Endoscopic Evaluation ◽

Severe Nausea ◽

Capsaicin Application ◽

Cannabinoid Hyperemesis Syndrome ◽

History Of ◽

Topical Capsaicin ◽

Cannabis Hyperemesis Syndrome

Introduction. Cannabinoid hyperemesis syndrome (CHS), associated with chronic cannabis use, presents with cyclic abdominal pain, nausea, and vomiting. With increasing use of marijuana, the incidence of CHS is expected to increase. Most patients with CHS make frequent visits to the emergency room and are usually refractory to conventional treatment. We, therefore, present a case of CHS successfully treated with topical capsaicin application. Case Presentation. A 41-year-old female with a recent excess use of cannabis presented to the emergency department for evaluation of recurrent excruciating epigastric pain accompanied by severe nausea and vomiting. She had similar, milder symptoms a year ago and underwent endoscopic evaluation which was negative except for mild reflux esophagitis for which she was started on a proton pump inhibitor. On this presentation, basic laboratory workup, EKG, and CT scan of abdomen and pelvis were unremarkable. A detailed abdominal exam was only positive for mild epigastric tenderness. She was instructed to continue pantoprazole and pain medication and outpatient repeat esophagogastroduodenoscopy. The patient returned the next day with extreme retching, nausea, and vomiting and was admitted for further evaluation. Intravenous fluids, antiemetics, and morphine were started for pain control with no symptomatic improvement. A diagnosis of cannabis hyperemesis syndrome was made based on history of chronic marijuana use and otherwise negative workup. A trial of topical capsaicin, over the epigastric region, was tried that provided dramatic relief within 24 hours. Repeat endoscopic evaluation had no evidence of ulcers, celiac disease, or esophagitis. She was discharged on topical capsaicin and counselled on marijuana abstinence, with no return of symptoms. Conclusion. Based on the dramatic resolution of symptoms with topical capsaicin, our case supports this promising intervention and provides an alternate approach to antiemetics and narcotics routinely used in patients with cannabis hyperemesis syndrome.

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