One size does not fit all: towards optimising the therapeutic potential of endogenous pain modulatory systems

Bannister, Kirsty; Hughes, Sam

doi:10.1097/j.pain.0000000000002697

Cited by 13 publications

(4 citation statements)

References 77 publications

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“…However, given the complexity and interrelatedness of these mechanisms, it is unlikely that one test will offer sufficient sensitivity and specificity for all patients. CPM is suggested to test the integrity of DNIC mechanisms only, so is unlikely to be informative of alterations in other descending control systems, such as those involved in stress-induced analgesia 11▪▪ . Other psychophysical tests, including quantitative sensory testing (QST) offset analgesia or temporal summation of pain 18–21 offer varying levels of sensitivity to detect pathology in different pain phenotypes, but they are similarly unlikely to be sufficient in isolation, nor are they expressly intended to probe descending control mechanisms.…”

Section: Endogenous Pain Control and Novel Avenues For Pharmacotherapymentioning

confidence: 99%

“…It was first recognised in the late 1970s that the brain and brainstem provide inhibitory/facilitatory control over incoming signals from the body, ultimately exerting their influence at the dorsal horn of the spinal cord. Since those early descriptions of diffuse noxious inhibitory controls (DNIC) 10 , multiple descending control mechanisms have been identified that interact to influence moment-to-moment pain experiences, depending on other competing internal and external demands 11▪▪ . Multiple neurotransmitter systems underpin these inhibitory/facilitatory influences, including gamma-aminobutyric acid (GABA), noradrenaline, serotonin and dopamine, in addition to opioidergic mechanisms 12 , offering candidate mechanisms for therapeutic intervention.…”

Section: Endogenous Pain Control and Novel Avenues For Pharmacotherapymentioning

confidence: 99%

“…As expected, subjectively reported pain decreased when participants were distracted by the task, but only following dosing with placebo or reboxetine; naltrexone abolished this effect. fMRI responses to varying intensities of thermal stimuli were identified in brain regions commonly associated with evoked pain experiences 36 , but also in midbrain and brainstem descending pain control networks under known opioidergic (reviewed in Fields 37 ) and noradrenergic control 11▪▪ . Spinal fMRI responses to differing heat intensities were reported at cervical levels C5/C6, corresponding to the appropriate dermatomal distributions of the forearm in the cord.…”

Section: In-vivo Assessment Of Descending Modulation In the Spinal Co...mentioning

confidence: 99%

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Harnessing the power of endogenous pain control mechanisms for novel therapeutics: how might innovations in neuroimaging help?

Howard

Lawn

Kowalczyk

2023

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of review This review explores the potential of using novel imaging approaches to deepen our understanding of descending modulatory mechanisms in pain, focussing on functional magnetic resonance imaging (fMRI) of the spinal cord and novel approaches to combining molecular and fMRI data. This review sheds light on the neural processes involved in pain modulation, paving the way for the development of targeted treatments. Recent findings The reviewed literature demonstrates significant advancements in pain research. Recent studies show the potential of using fMRI to investigate the spinal cord’s role in pain modulation. Furthermore, novel analytical approaches integrating molecular and fMRI data show promise in elucidating the complex neurobiological processes underlying pain regulation. The main themes explored here include the identification of neurochemical markers associated with pain modulation and the characterisation of neural circuits involved in descending pain control. Summary A comprehensive understanding of descending modulatory mechanisms in pain can inform the development of novel treatments, targeting dysfunction of these key pathways. By leveraging spinal fMRI and integrating molecular data into brain fMRI, researchers can identify potential therapeutic targets throughout the neuraxis. These advances may contribute to the development of personalised medicine approaches, allowing for tailored interventions based on individual pain profiles.

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Section: Endogenous Pain Control and Novel Avenues For Pharmacotherapymentioning

confidence: 99%

Section: Endogenous Pain Control and Novel Avenues For Pharmacotherapymentioning

confidence: 99%

Section: In-vivo Assessment Of Descending Modulation In the Spinal Co...mentioning

confidence: 99%

See 1 more Smart Citation

Harnessing the power of endogenous pain control mechanisms for novel therapeutics: how might innovations in neuroimaging help?

Howard

Lawn

Kowalczyk

2023

Current Opinion in Supportive &Amp; Palliative Care

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“…To address this gap, we aimed at investigating the relationship between use of CIHA and placebo effects given the potential therapeutic prospective of endogenous pain modulation in chronic pain management (Bannister & Hughes, 2022). It should be noted that efficacy of CIHA is beyond the scope of this study.…”

Section: Introductionmentioning

confidence: 99%

Yoga and massage are associated with small experimental placebo effects in chronic orofacial pain

Yin

Muhammed

Wang

et al. 2023

European Journal of Pain

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Background Complementary and Integrative Health Approaches (CIHA), including but not limited to, natural products and Mind and Body Practices (MBPs), are promising non‐pharmacological adjuvants to the arsenal of pain management therapeutics. We aim to establish possible relationships between use of CIHA and the capacity of descending pain modulatory system in the form of occurrence and magnitude of placebo effects in a laboratory setting. Methods This cross‐sectional study investigated the relationship between self‐reported use of CIHA, pain disability, and experimentally induced placebo hypoalgesia in chronic pain participants suffering from Temporomandibular Disorders (TMD). In the 361 enrolled TMD participants, placebo hypoalgesia was measured using a well‐established paradigm with verbal suggestions and conditioning cues paired with distinct heat painful stimulations. Pain disability was measured with the Graded Chronic Pain Scale, and use of CIHA were recorded with a checklist as part of the medical history. Results Use of physically oriented MBPs (e.g., yoga and massage) was associated with reduced placebo effects (F1,2110.44 = 23.15, p < 0.001, Cohen's d = 0.171). Further, linear regressions indicated that greater number of physically oriented MBPs predicted smaller placebo effects (β = −0.17, p = 0.002), and less likelihood of being a placebo responder (OR = 0.70, p = 0.004). Use of psychologically oriented MBPs and natural product were not associated with placebo effects magnitude and responsiveness. Conclusions Our findings suggest that use of physically oriented CIHA was associated with experimental placebo effects possibly through an optimized capability to recognize distinct somatosensorial stimulations. Future research is needed to understand the mechanisms underlying placebo‐induced pain modulation in CIHA users. Significance Chronic pain participants who use physically oriented mind–body practices, such as yoga and massage, demonstrated attenuated experimentally induced placebo hypoalgesia in comparison with those who do not use them. This finding disentangled the relationship between use of complementary and integrative approaches and placebo effects, providing the potential therapeutic perspective of endogenous pain modulation in chronic pain management.

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Gastrointestinal pain: A systematic review of temporal summation of pain paradigms and outcomes

Huisman,

Mansfield,

Cummins

et al. 2024

European Journal of Pain

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Background and ObjectiveSince targeted treatment for gastrointestinal pain is elusive, identifying the mechanistic underpinning of this pain type is important. Facilitation of spinal neuronal responses underpins certain pain types, and the psychophysical temporal summation of pain (TSP) paradigm provides a proxy measure of spinal facilitatory processes. Our aim was to systematically review whether facilitated TSP is a feature of gastrointestinal pain in patients with, or pain‐free people experiencing experimentally induced, gastrointestinal pain.Databases and Data TreatmentEMBASE, MEDLINE, PsychInfo, CINAHL, and Web of Science were systematically searched, from inception to July 2023, for human studies reporting TSP paradigm outcomes in the context of gastrointestinal pain. The Appraisal tool for Cross‐Sectional studies was used for quality assessment and applied independently by two researchers.ResultsFifteen papers consisting of cross‐sectional (n = 6), case–control (n = 8), and retrospective cohort (n = 1) studies, were included. Thirteen studies investigated TSP in people with gastrointestinal pain with (n = 5) or without (n = 8) defined pathology. Two studies evoked TSP by repetitive gut stimulation in people undergoing abdominal medical procedures. Preliminary evidence showed that facilitated TSP correlated with the presence of functional gastrointestinal pain in women, and those with a history of trauma. No effect was observed in people with inflammatory bowel disease, although it was often unclear if they experienced pain.ConclusionsIt is not possible to conclude whether facilitated TSP is a feature of gastrointestinal pain. We recommend that subgroup findings are corroborated and that TSP paradigms are standardized in order that direct comparisons between studies may be made.Significance StatementEvidence indicated that pain facilitatory processes, as evidenced by a facilitated TSP outcome, contribute to functional gastrointestinal pain in women and those with a history of trauma. However, heterogeneity of study populations and paradigms precluded statistical synthesis and findings would need be corroborated. Studies exploring facilitatory processes in people with inflammatory bowel diseases did not report significant results, but pain is not a given in these conditions and, conversely, may be driven by peripheral inflammation during active disease. This should be taken in consideration in future explorations.Registration ReviewPROSPERO CRD42022341845.

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One size does not fit all: towards optimising the therapeutic potential of endogenous pain modulatory systems

Cited by 13 publications

References 77 publications

Harnessing the power of endogenous pain control mechanisms for novel therapeutics: how might innovations in neuroimaging help?

Harnessing the power of endogenous pain control mechanisms for novel therapeutics: how might innovations in neuroimaging help?

Yoga and massage are associated with small experimental placebo effects in chronic orofacial pain

Gastrointestinal pain: A systematic review of temporal summation of pain paradigms and outcomes

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