Acetaminophen and pregabalin attenuate central sensitization in rodent models of nociplastic widespread pain

Yajima, Manami; Sugimoto, Mariko; Sugimura, Yae K.; Takahashi, Yukari; Kato, Fusao

doi:10.1016/j.neuropharm.2022.109029

Cited by 10 publications

(7 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Changes in the activity of these neurons have been demonstrated inacute inflammatory pain (Adedoyin et al, 2010 ; Sugimura et al, 2016 ; Shinohara et al, 2017 ; Miyazawa et al, 2018 ), in colitis (Han and Neugebauer, 2004 ), in muscle pain (Cheng et al, 2011 ), in neuropathic pain (Ikeda et al, 2007 ; Gonçalves and Dickenson, 2012 ; Nakao et al, 2012 ; Ji et al, 2017 ), and in arthritis pain models (Neugebauer and Li, 2003 ; Bird et al, 2005 ; Han et al, 2005 ; Li and Neugebauer, 2006 ; Ji and Neugebauer, 2007 , 2009 ; Fu and Neugebauer, 2008 ; Fu et al, 2008 ; Ji et al, 2009 ; Ren and Neugebauer, 2010 ; Ren et al, 2011 , 2013 ). Decreasing amygdala activity has been shown to inhibit pain-related behavior in arthritic (Han and Neugebauer, 2005 ; Ji et al, 2007 , 2010 ; Fu and Neugebauer, 2008 ; Palazzo et al, 2008 ; Ji and Neugebauer, 2009 ; Grégoire and Neugebauer, 2013 ; Ren et al, 2013 ; Medina et al, 2014 ; Thompson et al, 2015 ; Kim et al, 2017 ; Mazzitelli and Neugebauer, 2019 ; Mazzitelli et al, 2021 ), acute inflammatory (Kolber et al, 2010 ; Palazzo et al, 2011 ; Sugimoto et al, 2021 ), visceral (Crock et al, 2012 ), widespread nociplastic (Yajima et al, 2022 ), and neuropathic (Pedersen et al, 2007 ; Ansah et al, 2010 ; Jiang et al, 2014 ; Ji et al, 2017 ; Seno et al, 2018 ; Wilson et al, 2019 ; Mazzitelli et al, 2022 ) pain models.…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in CGRP Regulation and Function in the Amygdala in a Rat Model of Neuropathic Pain

Presto

Neugebauer

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

The amygdala has emerged as a key player in the emotional response to pain and pain modulation. The lateral and capsular regions of the central nucleus of the amygdala (CeA) represent the “nociceptive amygdala” due to their high content of neurons that process pain-related information. These CeA divisions are the targets of the spino-parabrachio-amygdaloid pain pathway, which is the predominant source of calcitonin gene-related peptide (CGRP) within the amygdala. Changes in lateral and capsular CeA neurons have previously been observed in pain models, and synaptic plasticity in these areas has been linked to pain-related behavior. CGRP has been demonstrated to play an important role in peripheral and spinal mechanisms, and in pain-related amygdala plasticity in male rats in an acute arthritis pain model. However, the role of CGRP in chronic neuropathic pain-related amygdala function and behaviors remains to be determined for both male and female rats. Here we tested the hypothesis that the CGRP1 receptor is involved in neuropathic pain-related amygdala activity, and that blockade of this receptor can inhibit neuropathic pain behaviors in both sexes. CGRP mRNA expression levels in the CeA of male rats were upregulated at the acute stage of the spinal nerve ligation (SNL) model of neuropathic pain, whereas female rats had significantly higher CGRP and CGRP receptor component expression at the chronic stage. A CGRP1 receptor antagonist (CGRP 8-37) administered into the CeA in chronic neuropathic rats reduced mechanical hypersensitivity (von Frey and paw compression tests) in both sexes but showed female-predominant effects on emotional-affective responses (ultrasonic vocalizations) and anxiety-like behaviors (open field test). CGRP 8-37 inhibited the activity of CeA output neurons assessed with calcium imaging in brain slices from chronic neuropathic pain rats. Together, these findings may suggest that CGRP1 receptors in the CeA are involved in neuropathic pain-related amygdala activity and contribute to sensory aspects in both sexes but to emotional-affective pain responses predominantly in females. The sexually dimorphic function of CGRP in the amygdala would make CGRP1 receptors a potential therapeutic target for neuropathic pain relief, particularly in females in chronic pain conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Sex Differences in CGRP Regulation and Function in the Amygdala in a Rat Model of Neuropathic Pain

Presto

Neugebauer

2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Another meta-analysis review of 10 randomized controlled trials, including 1712 patients with OA, found that while NSAIDs were more effective than paracetamol for pain relief, paracetamol was still effective [ 59 ]. Conversely, paracetamol in combination with weak opioids (eg, tramadol) has been proven to be effective in managing pain symptoms associated with OA [ 60 ]. In addition to being clinically ineffective in the treatment of LBP and OA, use of paracetamol can result in abnormal liver function test results compared with placebo [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…The conflicting evidence on the efficacy of paracetamol may, in part, be due to the different types of pain experienced by patients. Nociplastic pain, defined as pain occurring through altered nociception without nociceptor activation and nerve injury, is characterized by widespread pain through multiple body regions and often causes ongoing pain symptoms [ 60 ]. However, neuropathic pain is caused by nerve damage and often does not respond to certain medications.…”

Section: Discussionmentioning

confidence: 99%

Paracetamol Use in Patients With Osteoarthritis and Lower Back Pain: Infodemiology Study and Observational Analysis of Electronic Medical Record Data

Pickering¹,

Mezouar²,

Kechemir³

et al. 2022

JMIR Public Health Surveill

View full text Add to dashboard Cite

Background Lower back pain (LBP) and osteoarthritis (OA) are common musculoskeletal disorders and account for around 17.0% of years lived with disability worldwide; however, there is a lack of real-world data on these conditions. Paracetamol brands are frequently prescribed in France for musculoskeletal pain and include Doliprane, Dafalgan, and Ixprim (tramadol-paracetamol). Objective The objective of this retrospective study was to understand the journey of patients with LBP or OA when treated with paracetamol. Methods Three studies were undertaken. Two studies analyzed electronic medical records from general practitioners (GPs) and rheumatologists of patients with OA or LBP, who had received at least one paracetamol prescription between 2013 and 2018 in France. Data were extracted, anonymized, and stratified by gender, age, and provider specialty. The third study, an infodemiology study, analyzed associations between terms used on public medical forums and Twitter in France and the United States for OA only. Results In the first 2 studies, among patients with LBP (98,998), most (n=92,068, 93.0%) saw a GP, and Doliprane was a first-line therapy for 87.0% (n=86,128) of patients (71.0% [n=61,151] in combination with nonsteroidal anti-inflammatory drugs [NSAIDs] or opioids). Among patients with OA (99,997), most (n=84,997, 85.0%) saw a GP, and Doliprane was a first-line therapy for 83.0% (n=82,998) of patients (62.0% [n=51,459] in combination). Overall, paracetamol monotherapy prescriptions decreased as episodes increased. In the third study, in line with available literature, the data confirmed that the prevalence of OA increases with age (91.5% [212,875/232,650] above 41 years), OA is more predominant in females (46,530/232,650, 20.0%), and paracetamol use varies between GPs and rheumatologists. Conclusions This health surveillance analysis provides a better understanding of the journey for patients with LBP or OA. These data confirmed that although paracetamol remains the most common first-line analgesic for patients with LBP and OA, usage varies among patients and health care specialists, and there are concerns over efficacy.

show abstract

“…The mechanism of action of acetaminophen is unclear,166 but it most likely inhibits central cyclooxygenase activity and prostaglandin production 167. There is currently no evidence that acetaminophen (independent of combination therapy) reduces neuropathic pain,168 and very limited evidence via murine models that it improves nociplastic pain 169…”

Section: Chronification Of Pain In the Perioperative Settingmentioning

confidence: 99%

“…Although commonly prescribed for low back pain and sciatica, gabapentinoids are not effective for these conditions,199 and evidence is insufficient regarding central neuropathic pain syndromes (eg, poststroke pain) 202 203. There is limited evidence available regarding the efficacy of gabapentin for nociplastic pain syndromes,204 but there is data from murine models suggesting pregabalin may inhibit central sensitization pathways that propagate nociplastic pain 169 205. For fibromyalgia and other nociplastic conditions, there is stronger evidence for pregabalin 206 207…”

Section: Chronification Of Pain In the Perioperative Settingmentioning

confidence: 99%

Integrating mechanistic-based and classification-based concepts into perioperative pain management: an educational guide for acute pain physicians

Chen

Wang

Sites

et al. 2023

Reg Anesth Pain Med

View full text Add to dashboard Cite

Chronic pain begins with acute pain. Physicians tend to classify pain by duration (acute vs chronic) and mechanism (nociceptive, neuropathic and nociplastic). Although this taxonomy may facilitate diagnosis and documentation, such categories are to some degree arbitrary constructs, with significant overlap in terms of mechanisms and treatments. In clinical practice, there are myriad different definitions for chronic pain and a substantial portion of chronic pain involves mixed phenotypes. Classification of pain based on acuity and mechanisms informs management at all levels and constitutes a critical part of guidelines and treatment for chronic pain care. Yet specialty care is often siloed, with advances in understanding lagging years behind in some areas in which these developments should be at the forefront of clinical practice. For example, in perioperative pain management, enhanced recovery protocols are not standardized and tend to drive treatment without consideration of mechanisms, which in many cases may be incongruent with personalized medicine and mechanism-based treatment. In this educational document, we discuss mechanisms and classification of pain as it pertains to commonly performed surgical procedures. Our goal is to provide a clinical reference for the acute pain physician to facilitate pain management decision-making (both diagnosis and therapy) in the perioperative period.

show abstract

Acetaminophen and pregabalin attenuate central sensitization in rodent models of nociplastic widespread pain

Cited by 10 publications

References 49 publications

Sex Differences in CGRP Regulation and Function in the Amygdala in a Rat Model of Neuropathic Pain

Sex Differences in CGRP Regulation and Function in the Amygdala in a Rat Model of Neuropathic Pain

Paracetamol Use in Patients With Osteoarthritis and Lower Back Pain: Infodemiology Study and Observational Analysis of Electronic Medical Record Data

Integrating mechanistic-based and classification-based concepts into perioperative pain management: an educational guide for acute pain physicians

Contact Info

Product

Resources

About