scholarly journals Sex Differences in Tolerance to Delta-9-Tetrahydrocannabinol in Mice With Cisplatin-Evoked Chronic Neuropathic Pain

2021 ◽  
Vol 8 ◽  
Author(s):  
Angela N. Henderson-Redmond ◽  
LaTaijah C. Crawford ◽  
Diana E. Sepulveda ◽  
David E. Hale ◽  
Julia J. Lesperance ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sex Differences ◽  
Neuropathic Pain ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Preclinical Research ◽  
Chronic Neuropathic Pain ◽  
Analgesic Tolerance ◽  
Increased Sensitivity ◽  
Males And Females

Tolerance to the pain-relieving effects of cannabinoids limits the therapeutic potential of these drugs in patients with chronic pain. Recent preclinical research with rodents and clinical studies in humans has suggested important differences between males and females in the development of tolerance to cannabinoids. Our previous work found that male mice expressing a desensitization resistant form (S426A/S430A) of the type 1 cannabinoid receptor (CB1R) show delayed tolerance and increased sensitivity to the antinociceptive effects of delta-9-tetrahydrocannabinol (∆9-THC). Sex differences in tolerance have been reported in rodent models with females acquiring tolerance to ∆9-THC faster than males. However, it remains unknown whether the S426A/S430A mutation alters analgesic tolerance to ∆9-THC in mice with chemotherapy-evoked chronic neuropathic pain, and also whether this tolerance might be different between males and females. Male and female S426A/S430A mutant and wild-type littermates were made neuropathic using four once-weekly injections of 5 mg/kg cisplatin and subsequently assessed for tolerance to the anti-allodynic effects of 6 and/or 10 mg/kg ∆9-THC. Females acquired tolerance to the anti-allodynic effects of both 6 and 10 mg/kg ∆9-THC faster than males. In contrast, the S426A/S430A mutation did not alter tolerance to ∆9-THC in either male or female mice. The anti-allodynic effects of ∆9-THC were blocked following pretreatment with the CB1R antagonist, rimonabant, and partially blocked following pretreatment with the CB2R inverse agonist, SR144528. Our results show that disruption of the GRK/β-arrestin-2 pathway of desensitization did not affect sensitivity and/or tolerance to ∆9-THC in a chronic pain model of neuropathy.

Chronic neuropathic pain after traumatic peripheral nerve injuries in the upper extremity: prevalence, demographic and surgical determinants, impact on health and on pain medication

2019 ◽  
Vol 20 (1) ◽  
pp. 95-108
Author(s):  
Adriana Miclescu ◽  
Antje Straatmann ◽  
Panagiota Gkatziani ◽  
Stephen Butler ◽  
Rolf Karlsten ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Upper Extremity ◽  
Nerve Injury ◽  
Persistent Pain ◽  
Peripheral Nerve Injuries ◽  
Nerve Injuries ◽  
Chronic Neuropathic Pain ◽  
Younger Age

AbstractBackground and aimsAside from the long term side effects of a nerve injury in the upper extremity with devastating consequences there is often the problem of chronic neuropathic pain. The studies concerning the prevalence of persistent pain of neuropathic origin after peripheral nerve injuries are sparse. The prevalence and risk factors associated with chronic neuropathic pain after nerve injuries in the upper extremity were assessed.MethodsA standardized data collection template was employed prospectively and retrospectively for all patients with traumatic nerve injuries accepted at the Hand Surgery Department, Uppsala, Sweden between 2010 and 2018. The template included demographic data, pain diagnosis, type of injured nerve, level of injury, date of the lesion and repair, type of procedure, reoperation, time since the procedure, S-LANSS questionnaire (Self report-Leeds Assessment of Neuropathic Symptoms and Signs), RAND-36 (Item short form health survey), QuickDASH (Disability of Shoulder, Arm and Hand) and additional questionnaires concerned medication, pain intensity were sent to 1,051 patients with nerve injuries. Partial proportional odds models were used to investigate the association between persistent pain and potential predictors.ResultsMore than half of the patients undergoing a surgical procedure developed persistent pain. Prevalence of neuropathic pain was 73% of the patients with pain (S-LANSS ≥ 12 or more). Multivariate analysis indicated that injury of a major nerve OR 1.6 (p = 0.013), years from surgery OR 0.91 (p = 0.01), younger age OR 0.7 (p < 0.001), were the main factors for predicting pain after surgery. The type of the nerve injured was the strongest predictor for chronic pain with major nerves associated with more pain (p = 0.019).ConclusionsA high prevalence of chronic pain and neuropathic pain with a negative impact on quality of life and disability were found in patients after traumatic nerve injury. Major nerve injury, younger age and less time from surgery were predictors for chronic pain.

scholarly journals Dorsal Root Ganglion (DRG) and Chronic Pain

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Amnon A. Berger ◽  
Yao Liu ◽  
HarLee Possoit ◽  
Anna C. Rogers ◽  
Warner Moore ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Dorsal Root ◽  
Randomized Trials ◽  
Pain Treatment ◽  
Common Condition ◽  
Significant Morbidity ◽  
Chronic Neuropathic Pain

Context: Chronic neuropathic pain is a common condition, and up to 11.9% of the population have been reported to suffer from uncontrolled neuropathic pain. Chronic pain leads to significant morbidity, lowered quality of life, and loss of workdays, and thus carries a significant price tag in healthcare costs and lost productivity. dorsal root ganglia (DRG) stimulation has been recently increasingly reported and shows promising results in the alleviation of chronic pain. This paper reviews the background of DRG stimulation, anatomical, and clinical consideration and reviews the clinical evidence to support its use. Evidence Acquisition: The DRG span the length of the spinal cord and house the neurons responsible for sensation from the periphery. They may become irritated by direct compression or local inflammation. Glial cells in the DRG respond to nerve injury, producing inflammatory markers and contribute to the development of chronic pain, even after the resolution of the original insult. While the underlying mechanism is still being explored, recent studies explored the efficacy of DRG stimulation and neuromodulation for chronic pain treatment. Results: Several reported cases and a small number of randomized trials were published in recent years, describing different methods of DRG stimulation and neuromodulation with promising results. Though evidence quality is mostly low, these results provide evidence to support the utilization of this technique. Conclusions: Chronic neuropathic pain is a common condition and carries significant morbidity and impact on the quality of life. Recent evidence supports the use of DRG neuromodulation as an effective technique to control chronic pain. Though studies are still emerging, the evidence appears to support this technique. Further studies, including large randomized trials evaluating DRG modulation versus other interventional and non-interventional techniques, are needed to further elucidate the efficacy of this method. These studies are also likely to inform the patient selection and the course of treatment.

scholarly journals GPR171 Agonist Reduces Chronic Neuropathic and Inflammatory Pain in Male, but not in Female Mice

2021 ◽  
Author(s):  
Akila Ram ◽  
Taylor Edwards ◽  
Ashley McCarty ◽  
Leela Afrose ◽  
Max V McDermott ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Inflammatory Pain ◽  
Therapeutic Potential ◽  
Periaqueductal Gray ◽  
Male Mice ◽  
Once Daily ◽  
Female Mice ◽  
Protein Levels ◽  
Thermal Hypersensitivity

Chronic pain is a growing public health crisis that requires exigent and efficacious therapeutics. GPR171 is a promising therapeutic target that is widely expressed through the brain, including within the descending pain modulatory regions. Here, we explore the therapeutic potential of the GPR171 agonist, MS15203, in its ability to alleviate chronic pain in male and female mice using a once-daily systemic dose (10mg/kg, i.p.) of MS15203 over the course of 5 days. We found that in our models of Complete Freunds Adjuvant (CFA)-induced inflammatory pain and chemotherapy-induced peripheral neuropathy (CIPN), MS15203 did not reduce thermal hypersensitivity and allodynia, respectively, in female mice. On the other hand, MS15203 treatment decreased the duration of thermal hypersensitivity in CFA-treated male mice following 3 days of once-daily administration. MS15203 treatment also produced an improvement in allodynia in male mice, but not female mice, in neuropathic pain after 5 days of treatment. Gene expression of GPR171 and that of its endogenous ligand BigLEN, encoded by the gene PCSK1N, were unaltered within the periaqueductal gray in both male and female mice following inflammatory and neuropathic pain. However, following neuropathic pain in male mice, the protein levels of GPR171 were decreased in the periaqueductal gray. Treatment with MS15203 then rescued the protein levels of GPR171 in the periaqueductal gray of these mice. Taken together, our results identify GPR171 as a GPCR that displays sexual dimorphism in alleviation of chronic pain. Further, our results suggest that GPR171 and MS15203 have demonstrable therapeutic potential in the treatment of chronic pain.

scholarly journals Neuropathic pain

2021 ◽  
pp. 58-64
Author(s):  
V. A. Koriachkin ◽  
A. P. Spasova ◽  
V. V. Khinovker
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Correct Diagnosis ◽  
Epidemiological Studies ◽  
Chronic Neuropathic Pain ◽  
Official Document ◽  
Adequate Treatment ◽  
Pain Syndromes ◽  
Recent Classification

Background Chronic neuropathic pain is a common occurrence, its prevalence ranges from 7 to 10% of the total population. Currently, the only official document that includes neuropathic pain is the International Classification of Headaches Disorders (ICHD-3), in which this type of pain is associated with traumatic brain injury and neuralgia. Until now, there has been no generally accepted terminology and classification of chronic neuropathic pain.Objective To provide the current terminology, classification and additional characteristics of neuropathic chronic pain.Results The review of modern terminology and classification of neuropathic chronic pain describes the terms included in the concept of chronic peripheral and central neuropathic pain, identifies pain subtypes, as well as its additional characteristics such as the intensity of neuropathic pain, the severity of suffering and disability.Conclusions Thus, the presented recent classification of chronic neuropathic pain is an exhaustive list of the most common neuropathic pain syndromes. The inclusion of classification into clinical practice will help to draw attention to the problem of treatment of chronic neuropathic pain by WHO members, carrying out epidemiological studies and making a correct diagnosis, and therefore the appointment of adequate treatment methods.

scholarly journals Dorsal Root Ganglion Stimulation for the Management of Chronic Neuropathic Pain: A Retrospective Case Series during Four Years follow-up in a Single Center

2020 ◽  
Vol 13 (1) ◽  
pp. 35-41
Author(s):  
Alfonso Papa ◽  
Elisabetta Saracco ◽  
Maria Teresa Di Dato ◽  
Pietro Buonavolontà ◽  
Anna Maria Salzano ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Data Collection ◽  
Dorsal Root ◽  
Case Series ◽  
Chronic Neuropathic Pain ◽  
Neuropathic Pain Syndrome

Objectives: The dorsal root ganglion (DRG) is involved in the transduction of pain signals to the central nervous system (CNS) and undergoes a number of physiopathological changes during chronic pain. The purpose of this data collection was to evaluate the long-term safety and efficacy of DRG stimulation for the treatment of chronic pain and its impact on functional aspects. Materials and Methods: Forty-four subjects with non-reactive chronic neuropathic pain syndrome were implanted with DRG stimulation. Patients were evaluated at baseline as well as at 15, and 30 days, and at 3, 6, 12, 24, 36 and 48 months after medical intervention/surgery using the Visual Analogic Scale (VAS), which measures pain intensity, and the Oswestry Scale, for the estimation of disability (ODI). Results: After four years of simulation, VAS and ODI showed a statistically significant reduction throughout the follow-up period. The average pain relief obtained after 48 months of treatment was 74.1% ± 3.4. Conclusion: The results of this data collection demonstrate the feasibility of DRG stimulation, the correspondence between the clinical indications at the DRG implant and what is commonly found in the literature on this technique.(18,20) Patients defined as clinical responders to DRG stimulation and so implanted with definitive IPG showed a sustained and long term efficacy. Eight patients had previously been implanted with a traditional SCS without any clinically relevant efficacy; they were then explained for unsatisfactory results. Six of them (75%) were later implanted with DRG, with long-term effectiveness. Another advantage of this therapy is the absence of positional effects and lead migration. The adverse events proved to be independent of the anatomical level of insertion; moreover, this series of cases show a lower incidence of lead migration than reported in the literature. In summary, DRGs have been ignored for too long, probably due to the technical difficulty of reaching their deep, almost extra-spinal anatomical position.

scholarly journals GPR171 Agonist Reduces Chronic Neuropathic and Inflammatory Pain in Male, But Not Female Mice

2021 ◽  
Vol 2 ◽  
Author(s):  
Akila Ram ◽  
Taylor Edwards ◽  
Ashley McCarty ◽  
Leela Afrose ◽  
Max V. McDermott ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Inflammatory Pain ◽  
Therapeutic Potential ◽  
Male Mice ◽  
Once Daily ◽  
Male And Female ◽  
Female Mice ◽  
Protein Levels ◽  
Thermal Hypersensitivity

Chronic pain is a growing public health crisis that requires exigent and efficacious therapeutics. GPR171 is a promising therapeutic target that is widely expressed through the brain, including within the descending pain modulatory regions. Here, we explore the therapeutic potential of the GPR171 agonist, MS15203, in its ability to alleviate chronic pain in male and female mice using a once-daily systemic dose (10 mg/kg, i.p.) of MS15203 over the course of 5 days. We found that in our models of Complete Freund's Adjuvant (CFA)-induced inflammatory pain and chemotherapy-induced peripheral neuropathy (CIPN), MS15203 did not alleviate thermal hypersensitivity and allodynia, respectively, in female mice. On the other hand, MS15203 treatment decreased the duration of thermal hypersensitivity in CFA-treated male mice following 3 days of once-daily administration. MS15203 treatment also produced an improvement in allodynia in male mice, but not female mice, in neuropathic pain after 5 days of treatment. Gene expression of GPR171 and that of its endogenous ligand BigLEN, encoded by the gene PCSK1N, were unaltered within the periaqueductal gray (PAG) in both male and female mice following inflammatory and neuropathic pain. However, following neuropathic pain in male mice, the protein levels of GPR171 were decreased in the PAG. Treatment with MS15203 then rescued the protein levels of GPR171 in the PAG of these mice. Taken together, our results identify GPR171 as a GPCR that displays sexual dimorphism in alleviation of chronic pain. Further, our results suggest that GPR171 and MS15203 have demonstrable therapeutic potential in the treatment of chronic pain.

Recognition of the importance of neuropathic pain epidemiology

2018 ◽  
Author(s):  
Matthew Brown
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
General Population ◽  
Significant Proportion ◽  
Epidemiological Data ◽  
Current Treatment ◽  
Pecking Order ◽  
Chronic Neuropathic Pain ◽  
Healthcare Resources ◽  
Epidemiology Studies

The landmark paper discussed in this chapter is ‘Prevalence of chronic pain with neuropathic characteristics in the general population’, published by Bouhassira and Lantéri-Minet in 2008. Understanding the extent to which a specific condition affects a population is of great importance, for two main reasons. First, robust epidemiological data influences relevant legislators and policymaking, leading to improvements in the allocation of scarce healthcare resources. Second, epidemiology studies alert clinicians and academics to deficiencies and oversights in current treatment. For decades, chronic pain resided in a twilight world, under-recognized and under-resourced, while patients suffered. Papers such as this pioneering work by Bouhassira and Lantéri-Minet started to turn the tide with respect to chronic pain’s profile in the pathological pecking order. It is important because it demonstrated in unarguable fashion the degree to which chronic neuropathic pain blights the lives of a significant proportion of the population.

Abstract 302: Chronic Neuropathic Pain Increases Susceptibility to Myocardial Ischemia/Reperfusion Injury by Sirt1 Carbonylative Inactivation

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Chen Li ◽  
Jingrun Yang ◽  
Lu Yu ◽  
Chunhu Gu ◽  
Heng Ma
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Carbonyl Stress ◽  
Ampk Activation ◽  
Chronic Neuropathic Pain ◽  
Myocardial Ischemia Reperfusion ◽  
Reactive Aldehyde

Pain is not a symptom that exists alone, but whether chronic pain enhances susceptibility to myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanisms remain unknown. Reactive aldehydes contribute to pain pathologies and cardiac injury, suggesting that aldehyde dehydrogenase (ALDH2), which detoxifies aldehydes, may regulate chronic pain related MI/R injury. In this study, chronic neuropathic pain was induced by chronic compression of the dorsal root ganglion (CCD). CCD for 2 weeks, ALDH2 KO or wild-type (WT) littermates were subjected to in vivo MI/R. CCD-WT mice exhibited heightened nociception and correlated with circulating aldehyde (4-HNE) accumulation and cardiac protein carbonylation. CCD induced 4-HNE overload provoked cardiac SIRT1 carbonylative inactivation and impairment the cardioprotection of LKB1-mediated AMPK activation, which resulting in enhanced MI/R injury and higher mortality compare with pain free WT mice. Chronic neuropathic pain enhanced susceptibility to MI/R injury was further exacerbated by ALDH2 deficiency in which associated with more impaired SIRT1-LKB1-AMPK signaling. However, treatment of CCD-WT mice with ALDH2-selective activator (Alda-1) or cardiac specific ALDH2 upregulation by AAV9-cTNT-mediated gene delivery significantly reduced chronic neuropathic pain-induced SIRT1 carbonylative inactivation and decreased MI/R injury (minor infarct size, less apoptosis, and elevated cardiac function). These results strongly suggest that elevated reactive aldehyde concentration, like that observed in the presence of chronic pain, may render cardiomyocytes more susceptible to MI/R injury by SIRT1 carbonylative inactivation and impairment the cardioprotection of LKB1-mediated AMPK activation. ALDH2 activation blocked reactive aldehyde overproduction induced carbonyl stress and attenuated myocardial ischemic vulnerability in chronic pain individual. Keywords: chronic pain; myocardial ischemia/reperfusion; ALDH2; 4-HNE; carbonylation

scholarly journals ERK activation in noradrenergic and serotonergic brainstem nuclei in chronic pain upon noxious stimulation and antidepressants treatment

2009 ◽  
Vol 15 (S3) ◽  
pp. 7-8
Author(s):  
G. Borges ◽  
E. Berrocoso ◽  
A. Ortega-Alvaro ◽  
J. A. Micó ◽  
F. L. Neto
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Noxious Stimulation ◽  
Analgesic Action ◽  
Chronic Neuropathic Pain ◽  
Erk Activation ◽  
Pain Transmission ◽  
Extracellular Signal ◽  
Brainstem Nuclei

AbstractChronic neuropathic pain is a pathology that affects thousands of people worldwide. Antidepressants have been prescribed for the treatment of this sort of pain but the mechanisms underlying their analgesic action remain unknown. Extracellular-signal regulated kinases (ERKs) are being implicated in pain transmission and modulation as well as in the pathophysiology of depression. In order to clarify some of the mechanisms which might be related to the analgesic effect of antidepressants, we started by evaluating possible changes in the pattern of activation of ERKs in rats with chronic constriction injury (CCI), an experimental model of chronic

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