scholarly journals Asprosin, a Novel Therapeutic Candidate for Painful Neuropathy: An Experimental Study in Mice

2021 ◽  
Author(s):  
Sibel Ozcan ◽  
Muhammed Mirac Kelestemur ◽  
Munevver Gizem Hekim ◽  
Ozgur Bulmus ◽  
Ferah Bulut ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Clinical Utility ◽  
Painful Neuropathy ◽  
Hot Plate ◽  
Clear Cut ◽  
Pain Models ◽  
Chronic Pain Conditions ◽  
Thermal Hypersensitivity ◽  
Novel Therapeutic

Abstract Neuropathic pain is primarily caused by nervous system lesions or dysfunction. Evidence strongly suggests that obesity, diabetes and cancer are common in chronic pain conditions, and pain complaints are common in these individuals. Recent studies indicate presence of a strong link between adipokines and neuropathic pain. However, the effects of asprosin, a novel adipokine, on neuropathic pain have not been studied in animal modelsMouse models were employed to investigate the antinociceptive effectiveness of asprosin in the treatment of three types of neuropathic pain, with metabolic (streptozocin/STZ), toxic (oxaliplatin/OXA), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, respectively. Changes in nociceptive behaviors were assessed relative to controls using thermal (the hot plate and cold plate tests, at 50 °C and 4 °C respectively) and mechanical pain (Von Frey test) tests at baseline and 30, 60, 120 and 180 minutes after asprosin administration. Serum level of asprosin was quantified by ELISA. In all three neuropathic pain models (STZ, OXA and CCI), asprosin administration significantly reduced both mechanical and thermal hypersensitivity, indicating that it exhibits a clear-cut antihypersensitivity effect in the analyzed neuropathic pain models. Asprosin levels were significantly lower in three types of neuropathic pain compare to controls (p < 0.05). The results yielded by the present study suggest that asprosin exhibits an analgesic effect in the neuropathic pain models and may have clinical utility in alleviating chronic pain associated with disease and injury originating from peripheral structures.

scholarly journals Pathogenic Role of iNOs+ M1 Effector Macrophages in Fibromyalgia

2020 ◽  
Author(s):  
Vishwas Tripathi ◽  
Amaresh Mishra ◽  
Yamini Pathak ◽  
Aklank Jain ◽  
Hridayesh Prakash
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Neurodegenerative Disorder ◽  
Specific Treatment ◽  
The Body ◽  
World Population ◽  
Pain Models ◽  
Chronic Pain Conditions ◽  
Inflammatory Macrophages ◽  
The Impact

Fibromyalgia (FM) or Fibromyalgia Syndrome (FMS) is a neurodegenerative disorder causing musculoskeletal pain, tenderness, stiffness, fatigue, and sleep disorder in the body. It is one of the most common chronic pain conditions, affecting about 6% of the world population. Being refractory, till date, no specific treatment of this disease is available. Accumulating evidences over the last few decades indicate that proinflammatory macrophages, cytokines, & chemokines as the key players in this disease. Recent findings suggest activation of Microglial cells and associated pro-inflammatory signals as one of the major causes of chronic pain in patients suffering from fibromyalgia. Increased density of iNOs/CD68+ M1 effector macrophages has been associated with neuropathic pain models. In light of this, depletion of these pro-inflammatory macrophages has been shown to reduce sensitivity to neuropathic pain. On the other hand, modulating pattern of AGEs (Advanced Glycation End-Products) can also contribute to inactivation of macrophages. These findings strongly suggest that macrophages are critical in both inflammatory and neuropathic pain. Therefore, this chapter highlights the impact of macrophage plasticity in various immunopathological aspects of fibromyalgia.

Neuropathic pain in patients with haemophilia, that is the question

2015 ◽  
Vol 35 (S 01) ◽  
pp. S5-S9 ◽  
Author(s):  
S. Krüger ◽  
T. Hilberg
Keyword(s):  
Rheumatoid Arthritis ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Differential Diagnosis ◽  
Pain Management ◽  
Pain Mechanisms ◽  
Number Of Patients ◽  
Paindetect Questionnaire ◽  
Chronic Disorders ◽  
Chronic Pain Conditions

SummaryChronic pain caused by recurrent joint bleedings affects a large number of patients with haemophilia (PwH). The basis of this pain, nociceptive or neuropathic, has not been investigated so far. In other pain-related chronic disorders such as osteoarthritis or rheumatoid arthritis, initial studies showed nociceptive but also neuropathic pain features. 137 PwH and 33 controls (C) completed the painDETECT-questionnaire (pDq), which identifies neuropathic components in a person´s pain profile. Based on the pDq results, a neuropathic pain component is classified as positive, negative or unclear. A positive neuropathic pain component was found in nine PwH, but not in C. In 20 PwH an unclear pDq result was observed. In comparison to C the allocation of pDq results is statistically significant (p≤0.001). Despite various pDq results in PwH and C a similar appraisal pain quality, but on a different level, was determined. Summarising the results, there is a potential risk to misunderstand underlying pain mechanisms in PwH. In chronic pain conditions based on haemophilic arthopathy, a differential diagnosis seems to be unalterable for comprehensive and individualised pain management in PwH.

Understanding transdermal buprenorphine and a practical guide to its use for chronic cancer and non-cancer pain management

2019 ◽  
Vol 15 (2) ◽  
pp. 147-158 ◽  
Author(s):  
Tony O’Brien, MB, FRCPI ◽  
Jin Seok Ahn, MD ◽  
Richard Chye, MBBS, FRACP, FFPMANZCA, FAChPM ◽  
Brian Le, MBBS (Hons), MPH, FRACP, FAChPM ◽  
Henry Lu, MD, DABPN, DPBPM ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Pain Management ◽  
Cancer Pain ◽  
Chronic Pain Management ◽  
Cancer Pain Management ◽  
Appropriate Use ◽  
Chronic Pain Conditions ◽  
Favorable Safety ◽  
Practical Recommendations

Transdermal buprenorphine (TDB) has demonstrated effectiveness in treating a range of chronic pain conditions, including cancer pain, nociceptive pain, and neuropathic pain and has a favorable safety profile. Worldwide, clinical experience of its use is relatively limited. There is considerable misunderstanding about the pharmacology, mechanism of action, and safety of buprenorphine. There is also limited guidance on the appropriate use of TDB for chronic pain management. This article presents an overview of TDB and also provides practical recommendations for its use as part of a multifaceted strategy in chronic cancer and non-cancer pain.

Efficacy and Safety of Antidepressants as Analgesics in Chronic Pain: A Review

2017 ◽  
Vol 41 (S1) ◽  
pp. S234-S234 ◽  
Author(s):  
J. Fennema ◽  
S. Petrykiv ◽  
L. de Jonge ◽  
M. Arts
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Low Back Pain ◽  
Back Pain ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Maximum Tolerated Dose ◽  
Health Concern ◽  
Low Back ◽  
Efficacy And Safety ◽  
Chronic Pain Conditions

IntroductionDue to the aging population worldwide, chronic pain is becoming an important public health concern. Chronic pain is bidirectional associated with psychiatric disorders including depression and anxiety. Antidepressants are widely used as adjuvant therapy for the treatment of chronic pain for many disorders.Objectives and aimsTo review available literature on the efficacy and safety of antidepressants for the treatment of chronic pain, including neuropathic pain, fibromyalgia, low back pain, and chronic headache or migraine.MethodsWe performed a detailed literature review through PubMed, EMBASE and Cochrane's Library to assess the efficacy and safety of antidepressants in chronic pain conditions.ResultsIn neuropathic pain, fibromyalgia, low back pain, and chronic headaches/migraine, tricyclic antidepressants (TCAs) showed a significant analgesic effect. Selective serotonin reuptake inhibitors (SSRIs) are not effective for the treatment of low back pain and headaches or migraine. Venlafaxine, a serotonin norepinephrine reuptake inhibitor (SNRI) showed significant improvement of fibromyalgia and neuropathic pain. Duloxetine (SNRI) also reduced the pain in fibromyalgia.ConclusionTCAs are the ‘gold standard’ antidepressant analgesics. However, an electrocardiogram and postural blood pressure should be implemented prior to TCA treatment and TCAs should be initiated at low dosages and subsequently increased to the maximum tolerated dose. One should pay attention to their cardiotoxic potential, especially in the older population. For the treatment of neuropathic pain, SNRIs are second-line agents. Although better tolerated, in most types of chronic pain conditions, the effectiveness of SSRIs is limited. To conclude: start low, go slow, and prescribe with caution.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Spinal NGF Restores Opioid Sensitivity in Neuropathic Rats: Possible Role of NGF as a Regulator of CCK-Induced Anti-Opioid Effects

2000 ◽  
Vol 5 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Catherine M Cahill ◽  
Terence J Coderre
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Nerve Injury ◽  
Postnatal Period ◽  
Spontaneous Pain ◽  
Pain Mechanisms ◽  
Nociceptive Neurons ◽  
Nociceptive Transmission ◽  
Chronic Pain Conditions ◽  
Injury Models

The breadth of peripheral effects produced by nerve growth factor (NGF) in nociceptive processing has been well documented. However, less is known about the functional significance of central NGF in nociceptive transmission. The effect of NGF on the nervous system is dependent on the developmental stage. During the prenatal developmental period, NGF is critical for survival of nociceptors; in the postnatal period it regulates the expression of nociceptor phenotype, and in the adult it contributes to pain following an inflammatory insult. The implications for central NGF in the expression and regulation of spinal neuropeptides that are involved in pain mechanisms are reviewed. Knowledge has been gained by studies using peripheral nerve injury models that cause a deprivation of central NGF. These models also give rise to the development of pain syndromes, which encompass spontaneous pain, hyperalgesia and allodynia, routinely referred to as neuropathic pain. These models provide an approach for examining the contribution of central NGF to nociceptive transmission. Chronic pain emanating from a nerve injury is typically refractory to traditional analgesics such as opioids. Recent evidence suggests that supplementation of spinal NGF restores morphine-induced antinociception in an animal model of neuropathic pain. This effect appears to be mediated by alterations in spinal levels of cholecystokinin. The authors hypothesize that NGF is critical in maintaining neurochemical homeostasis in the spinal cord of nociceptive neurons, and that supplementation may be beneficial in restoring and/or maintaining opioid analgesia in chronic pain conditions resulting from traumatic nerve injury.

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 Relief of neuropathic pain by cell-specific manipulation of nucleus accumbens dopamine D1- and D2-receptor-expressing neurons

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Daisuke Sato ◽  
Michiko Narita ◽  
Yusuke Hamada ◽  
Tomohisa Mori ◽  
Kenichi Tanaka ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Nucleus Accumbens ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
D2 Receptor ◽  
D1 Receptor ◽  
Cholinergic Interneurons ◽  
Chronic Pain Conditions ◽  
Stimulation Of

AbstractEmerging evidence suggests that the mesolimbic dopaminergic network plays a role in the modulation of pain. As chronic pain conditions are associated with hypodopaminergic tone in the nucleus accumbens (NAc), we evaluated the effects of increasing signaling at dopamine D1/D2-expressing neurons in the NAc neurons in a model of neuropathic pain induced by partial ligation of sciatic nerve. Bilateral microinjection of either the selective D1-receptor (Gs-coupled) agonist Chloro-APB or the selective D2-receptor (Gi-coupled) agonist quinpirole into the NAc partially reversed nerve injury-induced thermal allodynia. Either optical stimulation of D1-receptor-expressing neurons or optical suppression of D2-receptor-expressing neurons in both the inner and outer substructures of the NAc also transiently, but significantly, restored nerve injury-induced allodynia. Under neuropathic pain-like condition, specific facilitation of terminals of D1-receptor-expressing NAc neurons projecting to the VTA revealed a feedforward-like antinociceptive circuit. Additionally, functional suppression of cholinergic interneurons that negatively and positively control the activity of D1- and D2-receptor-expressing neurons, respectively, also transiently elicited anti-allodynic effects in nerve injured animals. These findings suggest that comprehensive activation of D1-receptor-expressing neurons and integrated suppression of D2-receptor-expressing neurons in the NAc may lead to a significant relief of neuropathic pain.

scholarly journals Ketamine for Non-Neuropathic Pain

2021 ◽  
Author(s):  
Subbulakshmi Sundaram ◽  
Ashok Swaminathan Govindarajan
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Complex Regional Pain Syndrome ◽  
Antinociceptive Effect ◽  
Pain Syndrome ◽  
Well Being ◽  
Pain Mechanisms ◽  
Cardiovascular Side Effects ◽  
Chronic Pain Conditions ◽  
Rescue Agent

Chronic pain is one of the leading causes of years lost to disability, as most of the time it is refractory to conventional treatment. Recent advances in understanding the pain mechanisms have favored the use of ketamine as a rescue agent in refractory chronic pain conditions, as it has potential modulating effect on both sensory-discriminative and affective motivational components of pain. Preclinical studies also suggested the antinociceptive effect of sub anesthetic dose of ketamine against central and peripheral neuropathic pain conditions and non-neuropathic pain conditions such as inflammatory and nociceptive pain states. Subanesthetic infusion of ketamine along with adjuvants such as midazolam and clonidine is found to reduce the psychomimetic and cardiovascular side effects of ketamine. Even though the consensus guidelines for intravenous use of ketamine for chronic pain advocate the use of ketamine only for complex regional pain syndrome, various other clinical studies suggested its role in other refractory painful conditions. Hence the present topic focuses specifically on the effect of ketamine on non-neuropathic pain conditions such as complex regional pain syndrome, fibromyalgia, headache, ischemic limb pain, etc. Many studies had shown that ketamine not only reduces the pain scores but also the analgesic medications, which further improves the well-being and quality of life.

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.

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