Cerebral analgesic response to non-steroidal anti-inflammatory drug ibuprofen

Duncan J Hodkinson; Nadine Khawaja; Owen O'Daly; Michael Thacker; Fernando O Zelaya; Caroline L Wooldridge; Tara Renton; Steven C R Williams; Matthew A Howard

doi:10.1097/j.pain.0000000000000176

Cerebral analgesic response to non-steroidal anti-inflammatory drug ibuprofen

Duncan J Hodkinson, Nadine Khawaja, Owen O'Daly, Michael Thacker, Fernando O Zelaya, Caroline L Wooldridge, Tara Renton, Steven C R Williams, Matthew A Howard

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

Abstract

Non-opioid agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the anti-hyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in pre- and post-surgical states, and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction (TME), and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales (VAS) inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized, double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow (rCBF) under pain-free conditions (pre-surgery). However, in the post-surgical state, we observed increased activation of top-down modulatory circuits which was accompanied by decreases in the areas engaged due to ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain-relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Original language	English
Pages (from-to)	1301-1310
Number of pages	10
Journal	Pain
Volume	156
Issue number	7
DOIs	https://doi.org/10.1097/j.pain.0000000000000176
Publication status	Published - Jul 2015

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title = "Cerebral analgesic response to non-steroidal anti-inflammatory drug ibuprofen",

abstract = "Non-opioid agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the anti-hyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in pre- and post-surgical states, and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction (TME), and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales (VAS) inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized, double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow (rCBF) under pain-free conditions (pre-surgery). However, in the post-surgical state, we observed increased activation of top-down modulatory circuits which was accompanied by decreases in the areas engaged due to ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain-relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.",

author = "Hodkinson, {Duncan J} and Nadine Khawaja and Owen O'Daly and Michael Thacker and Zelaya, {Fernando O} and Wooldridge, {Caroline L} and Tara Renton and Williams, {Steven C R} and Howard, {Matthew A}",

year = "2015",

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AU - Hodkinson, Duncan J

AU - Khawaja, Nadine

AU - O'Daly, Owen

AU - Thacker, Michael

AU - Zelaya, Fernando O

AU - Wooldridge, Caroline L

AU - Renton, Tara

AU - Williams, Steven C R

AU - Howard, Matthew A

PY - 2015/7

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N2 - Non-opioid agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the anti-hyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in pre- and post-surgical states, and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction (TME), and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales (VAS) inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized, double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow (rCBF) under pain-free conditions (pre-surgery). However, in the post-surgical state, we observed increased activation of top-down modulatory circuits which was accompanied by decreases in the areas engaged due to ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain-relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

AB - Non-opioid agents, such as non-steroidal anti-inflammatory drugs (NSAIDs), are the most commonly used class of analgesics. Increasing evidence suggests that cyclooxygenase (COX) inhibition at both peripheral and central sites can contribute to the anti-hyperalgesic effects of NSAIDs, with the predominant clinical effect being mediated centrally. In this study, we examined the cerebral response to ibuprofen in pre- and post-surgical states, and looked at the analgesic interaction between surgical state and treatment. We used an established clinical pain model involving third molar extraction (TME), and quantitative arterial spin labelling (ASL) imaging to measure changes in tonic/ongoing neural activity. Concurrent to the ASL scans, we presented visual analogue scales (VAS) inside the scanner to evaluate the subjective experience of pain. This novel methodology was incorporated into a randomized, double-blind placebo-controlled design, with an open method of drug administration. We found that independent of its antinociceptive action, ibuprofen has no effect on regional cerebral blood flow (rCBF) under pain-free conditions (pre-surgery). However, in the post-surgical state, we observed increased activation of top-down modulatory circuits which was accompanied by decreases in the areas engaged due to ongoing pain. Our findings demonstrate that ibuprofen has a measurable analgesic response in the human brain, with the subjective effects of pain-relief reflected in two distinct brain networks. The observed activation of descending modulatory circuits warrants further investigation, as this may provide new insights into the inhibitory mechanisms of analgesia that might be exploited to improve safety and efficacy in pain management.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

U2 - 10.1097/j.pain.0000000000000176

DO - 10.1097/j.pain.0000000000000176

M3 - Article

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VL - 156

SP - 1301

EP - 1310

JO - Pain

JF - Pain

IS - 7

ER -

Cerebral analgesic response to non-steroidal anti-inflammatory drug ibuprofen

Abstract

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