title: 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.
abstract: The discovery of transient receptor potential (TRP) receptors has advanced understanding of temperature sensation, and pre-clinical studies have identified TRP as major novel analgesic targets in inflammatory and neuropathic pain states. We systematically investigated the sensory effects and interactions of TRP agonists capsaicin (TRPV1), menthol (TRPM8) and cinnamaldehyde (TRPA1) applied topically to the skin in 14 healthy human participants. Capsaicin lowered heat pain thresholds while warm detection thresholds were unchanged, suggesting an effect purely on nociceptor nerve fibres. The amplitude of contact heat-evoked potentials (CHEP) and evoked pain ratings were negatively correlated after capsaicin, whereas CHEP had been correlated positively without capsaicin in a previous volunteer study. Menthol caused cold hypersensitivity and cinnamaldehyde caused heat hypersensitivity, but neither had an effect on evoked potentials. The CHEP after application of capsaicin show features observed in some patients with painful neuropathy, and could provide a model for development of novel analgesics, particularly TRPV1 antagonists.
authors.affiliation: Peripheral Neuropathy Unit, Imperial College London, Area A, Ground Floor, Hammersmith Hospital, Du Cane Rd, London W12 ONN, United Kingdom.
authors.forename: K
authors.initials: K
authors.lastname: Roberts
authors.forename: R
authors.initials: R
authors.lastname: Shenoy
authors.forename: P
authors.initials: P
authors.lastname: Anand
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D000328:Adult; D002211:Capsaicin / Q000008:administration & dosage / Q000633:toxicity; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006358:Hot Temperature; D006805:Human Experimentation; D006801:Humans; D008297:Male; D008610:Menthol / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D008954:Models, Biological; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D018689:Sensory System Agents / Q000008:administration & dosage / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000294:innervation; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D018689:Sensory System Agents; D050051:Transient Receptor Potential Channels; D008610:Menthol; D000171:Acrolein; D002211:Capsaicin; C012843:cinnamaldehyde