Impairment in Pain Perception in Adult Rats Lesioned as Neonates with 5.7-Dihydroxytryptamine

Muchacki, Rafał; Szkilnik, Ryszard; Malinowska-Borowska, Jolanta; Żelazko, Aleksandra; Lewkowicz, Łukasz; Nowak, Przemysław

doi:10.17219/acem/23362

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…Second, the different targets contained in the PAG shown here to be involved in the analgesic effect of paracetamol (CB 1 and mGlu 5 receptors, TRPV1 channels) induced an analgesic effect when directly activated in the PAG, this effect being exerted through the activation of the bulbospinal pathways (de Novellis et al, ; Maione et al, , ; Palazzo et al, ; Starowicz et al, ). Additionally, injury to these pathways and particularly to the pathways using 5‐HT, reduced the analgesic effect of paracetamol in animals (Dogrul et al, ; Muchacki et al, ; Pini et al, ; Tjolsen et al, ), and their involvement in the analgesic effect of paracetamol has been demonstrated in humans (Pickering et al, ). Finally, a spinal involvement (suspected to be indirect) in the analgesic effect of paracetamol has been shown in animals: paracetamol reduces c‐Fos labelling in the dorsal horn of the spinal cord in animal models of inflammatory pain (Abbadie & Besson, ; Honoré et al, ), and its analgesic effect is reduced by the inhibition of different spinal 5‐HT receptors (Alloui et al, ; Bonnefont et al, ; Courade, Chassaing, Bardin, Alloui, & Eschalier, , Courade, Caussade, et al, ).…”

Section: Discussionmentioning

confidence: 99%

Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey

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Dalmann

et al. 2020

British J Pharmacology

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Background and Purpose We previously demonstrated that paracetamol has to be metabolised in the brain by fatty acid amide hydrolase enzyme into AM404 (N‐(4‐hydroxyphenyl)‐5Z,8Z,11Z,14Z‐eicosatetraenamide) to activate CB1 receptors and TRPV1 channels, which mediate its analgesic effect. However, the brain mechanisms supporting paracetamol‐induced analgesia remain unknown. Experimental Approach The effects of paracetamol on brain function in Sprague‐Dawley rats were determined by functional MRI. Levels of neurotransmitters in the periaqueductal grey (PAG) were measured using in vivo 1H‐NMR and microdialysis. Analgesic effects of paracetamol were assessed by behavioural tests and challenged with different inhibitors, administered systemically or microinjected in the PAG. Key Results Paracetamol decreased the connectivity of major brain structures involved in pain processing (insula, somatosensory cortex, amygdala, hypothalamus, and the PAG). This effect was particularly prominent in the PAG, where paracetamol, after conversion to AM404, (a) modulated neuronal activity and functional connectivity, (b) promoted GABA and glutamate release, and (c) activated a TRPV1 channel‐mGlu5 receptor‐PLC‐DAGL‐CB1 receptor signalling cascade to exert its analgesic effects. Conclusions and Implications The elucidation of the mechanism of action of paracetamol as an analgesic paves the way for pharmacological innovations to improve the pharmacopoeia of analgesic agents.

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Section: Discussionmentioning

confidence: 99%

Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey

Barrière

Boumezbeur

Dalmann

et al. 2020

British J Pharmacology

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“…The dissociative anesthetics ketamine induces analgesic effects in models of acute pain and relieves thermal and mechanical allodynia in a chronic neuropathic pain model [125]. The involvement of the serotonergic neurotransmission in analgesic actions has been studied using neuropathic pain models in rats [126]. The gender difference in pain sensation and emotional domain has been reported using the transgenic mouse model of Alzheimer's disease [127].…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

Co-Players in Chronic Pain: Neuroinflammation and the Tryptophan-Kynurenine Metabolic Pathway

et al. 2021

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Chronic pain is an unpleasant sensory and emotional experience that persists or recurs more than three months and may extend beyond the expected time of healing. Recently, nociplastic pain has been introduced as a descriptor of the mechanism of pain, which is due to the disturbance of neural processing without actual or potential tissue damage, appearing to replace a concept of psychogenic pain. An interdisciplinary task force of the International Association for the Study of Pain (IASP) compiled a systematic classification of clinical conditions associated with chronic pain, which was published in 2018 and will officially come into effect in 2022 in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11) by the World Health Organization. ICD-11 offers the option for recording the presence of psychological or social factors in chronic pain; however, cognitive, emotional, and social dimensions in the pathogenesis of chronic pain are missing. Earlier pain disorder was defined as a condition with chronic pain associated with psychological factors, but it was replaced with somatic symptom disorder with predominant pain in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in 2013. Recently clinical nosology is trending toward highlighting neurological pathology of chronic pain, discounting psychological or social factors in the pathogenesis of pain. This review article discusses components of the pain pathway, the component-based mechanisms of pain, central and peripheral sensitization, roles of chronic inflammation, and the involvement of tryptophan-kynurenine pathway metabolites, exploring the participation of psychosocial and behavioral factors in central sensitization of diseases progressing into the development of chronic pain, comorbid diseases that commonly present a symptom of chronic pain, and psychiatric disorders that manifest chronic pain without obvious actual or potential tissue damage.

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Intrathecally injected tramadol reduces articular incapacitation and edema in a rat model of lipopolysaccharide (LPS)-induced reactive arthritis

et al. 2019

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Impairment in Pain Perception in Adult Rats Lesioned as Neonates with 5.7-Dihydroxytryptamine

Cited by 4 publications

References 26 publications

Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey

Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey

Co-Players in Chronic Pain: Neuroinflammation and the Tryptophan-Kynurenine Metabolic Pathway

Intrathecally injected tramadol reduces articular incapacitation and edema in a rat model of lipopolysaccharide (LPS)-induced reactive arthritis

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