title: Functional MRI brain imaging studies using the Contact Heat Evoked Potential Stimulator (CHEPS) in a human volunteer topical capsaicin pain model.
abstract: Acute application of topical capsaicin produces spontaneous burning and stinging pain similar to that seen in some neuropathic states, with local hyperalgesia. Use of capsaicin applied topically or injected intradermally has been described as a model for neuropathic pain, with patterns of activation in brain regions assessed using functional magnetic resonance imaging (fMRI) and positron emission tomography. The Contact Heat Evoked Potential Stimulator (CHEPS) is a noninvasive clinically practical method of stimulating cutaneous A-delta nociceptors. In this study, topical capsaicin (1%) was applied to the left volar forearm for 15 minutes of twelve adult healthy human volunteers. fMRI scans and a visual analog pain score were recorded during CHEPS stimulation precapsaicin and postcapsaicin application. Following capsaicin application there was a significant increase in visual analog scale (mean ± standard error of the mean; precapsaicin 26.4 ± 5.3; postcapsaicin 48.9 ± 6.0; P < 0.0001). fMRI demonstrated an overall increase in areas of activation, with a significant increase in the contralateral insular signal (mean ± standard error of the mean; precapsaicin 0.434 ± 0.03; postcapsaicin 0.561 ± 0.07; P = 0.047). The authors of this paper recently published a study in which CHEPS-evoked A-delta cerebral potential amplitudes were found to be decreased postcapsaicin application. In patients with neuropathic pain, evoked pain and fMRI brain responses are typically increased, while A-delta evoked potential amplitudes are decreased. The protocol of recording fMRI following CHEPS stimulation after topical application of capsaicin could be combined with recording of evoked potentials to provide a simple, rapid, and robust volunteer model to develop novel drugs for neuropathic pain.
authors.affiliation: Peripheral Neuropathy Unit, Hammersmith Hospital, Imperial College London.
authors.forename: Ravikiran
authors.initials: R
authors.lastname: Shenoy
authors.forename: Katherine
authors.initials: K
authors.lastname: Roberts
authors.forename: Anastasia
authors.initials: A
authors.lastname: Papadaki
authors.forename: Donald
authors.initials: D
authors.lastname: McRobbie
authors.forename: Maarten
authors.initials: M
authors.lastname: Timmers
authors.forename: Theo
authors.initials: T
authors.lastname: Meert
authors.forename: Praveen
authors.initials: P
authors.lastname: Anand
references.citation: J Neurophysiol. 1999 Oct;82(4):1934-43
references.pmid: 10515983
references.citation: Brain. 2004 Jul;127(Pt 7):1606-15
references.pmid: 15128618
references.citation: J Physiol. 1992 Mar;448:749-64
references.pmid: 1593488
references.citation: Pain. 1991 Dec;47(3):285-294
references.pmid: 1784499
references.citation: Pain. 2002 Sep;99(1-2):323-31
references.pmid: 12237211
references.citation: Cereb Cortex. 2006 Sep;16(9):1289-95
references.pmid: 16280463
references.citation: PLoS Med. 2005 Jul;2(7):e164
references.pmid: 16013891
references.citation: Pain. 1999 May;81(1-2):135-45
references.pmid: 10353501
references.citation: Brain. 1989 Oct;112 ( Pt 5):1317-31
references.pmid: 2804614
references.citation: J Pain. 2003 Apr;4(3):122-8
references.pmid: 14622709
references.citation: Neuron. 2002 Jul 18;35(2):383-93
references.pmid: 12160755
references.citation: Pain. 2005 Apr;114(3):397-407
references.pmid: 15777865
references.citation: Pain. 2004 Oct;111(3):360-367
references.pmid: 15363880
references.citation: J Neurosci. 1998 Nov 1;18(21):8947-59
references.pmid: 9787000
references.citation: BMC Neurol. 2007 Aug 03;7:21
references.pmid: 17683543
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18195-200
references.pmid: 16330766
references.citation: J Pain. 2008 Jan;9(1):53-63
references.pmid: 17988951
references.citation: Brain. 1998 May;121 ( Pt 5):931-47
references.pmid: 9619195
references.citation: Br J Anaesth. 1995 Aug;75(2):157-68
references.pmid: 7577249
references.citation: Eur J Pain. 2001;5(4):363-71
references.pmid: 11743702
references.citation: Br J Pharmacol. 1981 Jul;73(3):755-8
references.pmid: 6166346
references.citation: BMC Anesthesiol. 2008 Dec 17;8:8
references.pmid: 19091117
references.citation: Lancet. 2000 Sep 2;356(9232):785-7
references.pmid: 11022922
references.citation: BMJ. 2004 Apr 24;328(7446):991
references.pmid: 15033881
references.citation: Neurosci Lett. 2001 Dec;316(2):79-82
references.pmid: 11742720
references.citation: Nature. 1997 Oct 23;389(6653):816-24
references.pmid: 9349813
references.citation: Pain. 2004 Jul;110(1-2):318-28
references.pmid: 15275782
references.citation: Brain. 1994 Apr;117 ( Pt 2):385-96
references.pmid: 8186964
references.citation: Muscle Nerve. 1998 Dec;21(12):1661-7
references.pmid: 9843066
references.citation: J Clin Neurosci. 2011 Jul;18(7):926-32
references.pmid: 21550252
references.citation: Acta Neurol Taiwan. 2006 Sep;15(3):184-91
references.pmid: 16995598
references.citation: Pain. 2001 Apr;91(3):241-250
references.pmid: 11275380
references.citation: Brain. 2002 Jun;125(Pt 6):1326-36
references.pmid: 12023321
references.citation: J Pain Symptom Manage. 1998 Jul;16(1):10-20
references.pmid: 9707653
references.citation: Neuroimage. 2005 Dec;28(4):996-1006
references.pmid: 16112876
references.citation: Neurology. 1999 Aug 11;53(3):548-57
references.pmid: 10449119