The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli
Despite the explosion of interest in the genetic underpinnings of individual differences in pain sensitivity, conflicting findings have emerged for most of the identified "pain genes". Perhaps the prime example of this inconsistency is represented by catechol-O-methyltransferase (COMT), as...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/69040 |
| _version_ | 1826205550766981120 |
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| author | Loggia, Marco L. Jensen, Karin B. Wasan, Ajay D. Edwards, Robert R. Kong, Jian Gollub, Randy Lyanne |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Loggia, Marco L. Jensen, Karin B. Wasan, Ajay D. Edwards, Robert R. Kong, Jian Gollub, Randy Lyanne |
| author_sort | Loggia, Marco L. |
| collection | MIT |
| description | Despite the explosion of interest in the genetic underpinnings of individual differences in pain sensitivity, conflicting findings have emerged for most of the identified "pain genes". Perhaps the prime example of this inconsistency is represented by catechol-O-methyltransferase (COMT), as its substantial association to pain sensitivity has been reported in various studies, but rejected in several others. In line with findings from behavioral studies, we hypothesized that the effect of COMT on pain processing would become apparent only when the pain system was adequately challenged (i.e., after repeated pain stimulation). In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the brain response to heat pain stimuli in 54 subjects genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n 20, met/met = n 12). Met/met subjects exhibited stronger pain-related fMRI signals than val/val in several brain structures, including the periaqueductal gray matter, lingual gyrus, cerebellum, hippocampal formation and precuneus. These effects were observed only for high intensity pain stimuli after repeated administration. In spite of our relatively small sample size, our results suggest that COMT appears to affect pain processing. Our data demonstrate that the effect of COMT on pain processing can be detected in presence of 1) a sufficiently robust challenge to the pain system to detect a genotype effect, and/or 2) the recruitment of pain-dampening compensatory mechanisms by the putatively more pain sensitive met homozygotes. These findings may help explain the inconsistencies in reported findings of the impact of COMT in pain regulation. |
| first_indexed | 2024-09-23T13:14:56Z |
| format | Article |
| id | mit-1721.1/69040 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:14:56Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/690402022-10-01T13:58:57Z The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli Loggia, Marco L. Jensen, Karin B. Wasan, Ajay D. Edwards, Robert R. Kong, Jian Gollub, Randy Lyanne Harvard University--MIT Division of Health Sciences and Technology Gollub, Randy L. Gollub, Randy Lyanne Despite the explosion of interest in the genetic underpinnings of individual differences in pain sensitivity, conflicting findings have emerged for most of the identified "pain genes". Perhaps the prime example of this inconsistency is represented by catechol-O-methyltransferase (COMT), as its substantial association to pain sensitivity has been reported in various studies, but rejected in several others. In line with findings from behavioral studies, we hypothesized that the effect of COMT on pain processing would become apparent only when the pain system was adequately challenged (i.e., after repeated pain stimulation). In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the brain response to heat pain stimuli in 54 subjects genotyped for the common COMT val158met polymorphism (val/val = n 22, val/met = n 20, met/met = n 12). Met/met subjects exhibited stronger pain-related fMRI signals than val/val in several brain structures, including the periaqueductal gray matter, lingual gyrus, cerebellum, hippocampal formation and precuneus. These effects were observed only for high intensity pain stimuli after repeated administration. In spite of our relatively small sample size, our results suggest that COMT appears to affect pain processing. Our data demonstrate that the effect of COMT on pain processing can be detected in presence of 1) a sufficiently robust challenge to the pain system to detect a genotype effect, and/or 2) the recruitment of pain-dampening compensatory mechanisms by the putatively more pain sensitive met homozygotes. These findings may help explain the inconsistencies in reported findings of the impact of COMT in pain regulation. United States. National Institutes of Health (R01AT005280) United States. National Institutes of Health (R21AT00949) United States. National Institutes of Health (KO1AT003883) United States. National Institutes of Health (R21AT004497) National Center for Complementary and Alternative Medicine (U.S.) (PO1-AT002048) United States. National Institutes of Health (M01-RR-01066) United States. National Institutes of Health (UL1 RR025758-01) United States. National Institutes of Health (P41RR14075) United States. National Institutes of Health (DE-FG03-99ER62764) Swedish Society for Medical Research 2012-02-08T17:35:56Z 2012-02-08T17:35:56Z 2011-11 2011-04 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/69040 Loggia, Marco L. et al. “The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli.” Ed. Yu-Feng Zang. PLoS ONE 6.11 (2011): e27764. Web. 8 Feb. 2012. en_US http://dx.doi.org/10.1371/journal.pone.0027764 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Loggia, Marco L. Jensen, Karin B. Wasan, Ajay D. Edwards, Robert R. Kong, Jian Gollub, Randy Lyanne The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli |
| title | The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli |
| title_full | The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli |
| title_fullStr | The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli |
| title_full_unstemmed | The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli |
| title_short | The Catechol-O-Methyltransferase (COMT) val158met Polymorphism Affects Brain Responses to Repeated Painful Stimuli |
| title_sort | catechol o methyltransferase comt val158met polymorphism affects brain responses to repeated painful stimuli |
| url | http://hdl.handle.net/1721.1/69040 |
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