Activation of the descending pain modulatory system using cuff pressure algometry: Back translation from man to rat

Cummins, Tatum M.; Kucharczyk, M.; Graven‐Nielsen, Thomas; Bannister, Kirsty

doi:10.1002/ejp.1580

Cited by 36 publications

(45 citation statements)

References 28 publications

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“…For example, dysfunctional DNIC/CPM has previously been documented in chronic pain animal models and patients, and a beneficial therapeutic effect of pharmacological agents that manipulate noradrenergic transmission has been demonstrated [4,27]. Reassuringly, our recent study outlined that translatable mechanisms underlie endogenous inhibitory pathway expression [25]. In total therefore there is a clinical translational potential in regard to tailored pain pharmacotherapies in patients suffering from (metastatic) bone cancer.…”

Section: Discussionmentioning

confidence: 84%

“…Analogically to DNIC, CPM is pan-modal and it requires test and conditioning stimulus [22] and the conditioning stimulus must be noxious [23]. Recently, a novel approach has utilised two pressure cuffs controlled by a fully automated algometer [24] and there is evidence that a comparable noxious pressure paradigm activates the unique endogenous inhibitory control pathway in rats and humans [25].…”

Section: Discussionmentioning

confidence: 99%

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The Stage-Specific Plasticity of Descending Modulatory Controls in a Rodent Model of Cancer-Induced Bone Pain

Kucharczyk

Derrien

Dickenson

et al. 2020

Cancers

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Pain resulting from metastatic bone disease is a major unmet clinical need. Studying spinal processing in rodent models of cancer pain is desirable since the percept of pain is influenced in part by modulation at the level of the transmission system in the dorsal horn of the spinal cord. Here, a rodent model of cancer-induced bone pain (CIBP) was generated following syngeneic rat mammary gland adenocarcinoma cell injection in the tibia of male Sprague Dawley rats. Disease progression was classified as “early” or “late” stage according to bone destruction. Even though wakeful CIBP rats showed progressive mechanical hypersensitivity, subsequent in vivo electrophysiological measurement of mechanically evoked deep dorsal horn spinal neuronal responses revealed no change. Rather, a dynamic reorganization of spinal neuronal modulation by descending controls was observed, and this was maladaptive only in the early stage of CIBP. Interestingly, this latter observation corresponded with the degree of damage to the primary afferents innervating the cancerous tissue. Plasticity in the modulation of spinal neuronal activity by descending control pathways reveals a novel opportunity for targeting CIBP in a stage-specific manner. Finally, the data herein have translational potential since the descending control pathways measured are present also in humans.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

The Stage-Specific Plasticity of Descending Modulatory Controls in a Rodent Model of Cancer-Induced Bone Pain

Kucharczyk

Derrien

Dickenson

et al. 2020

Cancers

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“…Third, anesthesia can modulate the FC of the brain. We used a low dose of isoflurane during the fMRI scans that is widely employed in in vivo electrophysiology studies from the pain field (Cummins et al, 2020; Dickenson et al, 2020). The exposure to isoflurane during the scan was also shorter than standard in vivo techniques and did not require tracheal intubation.…”

Section: Discussionmentioning

confidence: 99%

Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats

et al. 2021

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Old age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre‐OA) and during the early and late phases of monosodium iodoacetate‐induced OA in rats. We then examined how sex and age affect longitudinal changes in PAG FC in OA. In a healthy state, females exhibited more widespread PAG FC than males, and this effect was exaggerated with aging. Young males had moderate PAG FC changes during the early phase but recruited additional brain regions, including the rostral anterior cingulate cortex (ACC), during the late phase. Young females exhibited widespread PAG FC in the early phase, which includes connections to insula, caudal ACC, and nucleus accumbens (NAc). Older groups had strong PAG FC with fewer regions in the early phase, but they recruited additional brain regions, including NAc, in the late phase. Overall, our findings show that PAG FC is modulated by sex and age in a healthy state. A widespread PAG network in the early phase of OA pain may contribute to the transition from acute to chronic OA pain and the increased risk of developing chronic pain for females. Enhanced PAG FC with the reward system may represent a potential mechanism underlying chronic OA pain in elderly patients.

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“…Analogically to DNIC, CPM is pan-modal and it requires test and conditioning stimulus [29] and the conditioning stimulus must be noxious [11]. Recently, a novel approach utilises two pressure cuffs controlled by a fully automated algometer [30] and there is evidence that a comparable noxious pressure paradigm activates the unique endogenous inhibitory control pathway in rat and man [13].…”

Section: Discussionmentioning

confidence: 99%

“…DNIC and its human counterpart conditioned pain modulation (CPM) is dysfunctional in rodent models of chronic pain and chronic pain patients respectively [9–12]. We propose that investigating the functionality of the DNIC pathway in CIBP rats is clinically relevant since pain phenotyping of patients with bone cancer pain has begun to include a measurement of CPM (ClinicalTrials.gov Identifier: NCT03908853) using a paradigm previously shown to translate between rodent and man [13].…”

Section: Introductionmentioning

confidence: 99%

The stage specific plasticity of descending modulatory controls in a rodent model of cancer induced bone pain

Kucharczyk

Derrien

Dickenson

et al. 2020

Preprint

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Pain resulting from metastatic bone disease is a major unmet clinical need. Studying spinal processing in rodent models of cancer pain is desirable since the percept of pain is influenced in part by modulation at the level of the transmission system in the dorsal horn of the spinal cord. Here a rodent model of cancer induced bone pain (CIBP) was generated following syngenic rat mammary gland adenocarcinoma cell injection in the tibia of male Sprague Dawley rats. Disease progression was classified as ′early′ or ′late′ stage according to bone destruction. Even though wakeful CIBP rats showed progressive mechanical hypersensitivity, subsequent in vivo electrophysiological measurement of mechanically evoked deep dorsal horn spinal neuronal responses revealed no change. Rather, a dynamic reorganization of spinal neuronal modulation by descending controls was observed, and this was maladaptive only in the early stage of CIBP. Interestingly, this latter observation corresponded with the degree of damage to the primary afferents innervating the cancerous tissue. Plasticity in the modulation of spinal neuronal activity by descending control pathways reveals a novel opportunity for targeting CIBP in a stage-specific manner. Finally, the data herein has translational potential since the descending control pathways measured are present also in man.

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Activation of the descending pain modulatory system using cuff pressure algometry: Back translation from man to rat

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 36 publications

References 28 publications

The Stage-Specific Plasticity of Descending Modulatory Controls in a Rodent Model of Cancer-Induced Bone Pain

The Stage-Specific Plasticity of Descending Modulatory Controls in a Rodent Model of Cancer-Induced Bone Pain

Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats

The stage specific plasticity of descending modulatory controls in a rodent model of cancer induced bone pain

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