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.

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 Experimentally induced pain does not influence updating of peripersonal space and body representations following tool-use

2018 ◽  
Author(s):  
Axel Davies Vittersø ◽  
Monika Halicka ◽  
Gavin Buckingham ◽  
Michael J Proulx ◽  
Mark Wilson ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Tool Use ◽  
Experimental Pain ◽  
Peripersonal Space ◽  
The Body ◽  
Body Representations ◽  
Tactile Target ◽  
The Difference ◽  
Chronic Pain Conditions ◽  
Crossmodal Congruency

Representations of the body and peripersonal space can be distorted for people with some chronic pain conditions. Experimental pain induction can give rise to similar, but transient distortions in healthy individuals. However, spatial and bodily representations are dynamic, and constantly update as we interact with objects in our environment. It is unclear whether induced pain disrupts the mechanisms involved in updating these representations. In the present study, we sought to investigate the effect of induced pain on the updating of peripersonal space and body representations during and following tool-use. We compared performance under three conditions (pain, active placebo, neutral) on a visuotactile crossmodal congruency task and a tactile distance judgement task to measure updating of peripersonal space and body representations, respectively. We induced pain by applying 1% capsaicin cream to the arm, and for placebo we used a gel that induced non-painful warming. Consistent with previous findings, the difference in crossmodal interference from visual distractors in the same compared to opposite visual field to the tactile target was less when tools were crossed than uncrossed. This suggests an extension of peripersonal space to incorporate the tips of the tools. Also consistent with previous findings, estimates of the felt distance between two points (tactile distance judgements) decreased after active tool-use. In contrast to our predictions, however, we found no evidence that pain interfered with performance on either task when compared to the control conditions. This suggests that the updating of peripersonal space and body representations is not disrupted by induced pain. Therefore, acute pain does not account for the distorted representations of the body and peripersonal space that can endure in people with chronic pain conditions.

scholarly journals Characterization of New TRPM8 Modulators in Pain Perception

2019 ◽  
Vol 20 (22) ◽  
pp. 5544 ◽  
Author(s):  
Carmen De Caro ◽  
Claudia Cristiano ◽  
Carmen Avagliano ◽  
Alessia Bertamino ◽  
Carmine Ostacolo ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Pain Perception ◽  
Transient Receptor Potential ◽  
Pain Modulation ◽  
The Body ◽  
Sprague Dawley ◽  
Transient Receptor Potential Melastatin ◽  
Pain Models ◽  
Excessive Activation

Background: Transient Receptor Potential Melastatin-8 (TRPM8) is a non-selective cation channel activated by cold temperature and by cooling agents. Several studies have proved that this channel is involved in pain perception. Although some studies indicate that TRPM8 inhibition is necessary to reduce acute and chronic pain, it is also reported that TRPM8 activation produces analgesia. These conflicting results could be explained by extracellular Ca2+-dependent desensitization that is induced by an excessive activation. Likely, this effect is due to phosphatidylinositol 4,5-bisphosphate (PIP2) depletion that leads to modification of TRPM8 channel activity, shifting voltage dependence towards more positive potentials. This phenomenon needs further evaluation and confirmation that would allow us to understand better the role of this channel and to develop new therapeutic strategies for controlling pain. Experimental approach: To understand the role of TRPM8 in pain perception, we tested two specific TRPM8-modulating compounds, an antagonist (IGM-18) and an agonist (IGM-5), in either acute or chronic animal pain models using male Sprague-Dawley rats or CD1 mice, after systemic or topical routes of administration. Results: IGM-18 and IGM-5 were fully characterized in vivo. The wet-dog shake test and the body temperature measurements highlighted the antagonist activity of IGM-18 on TRPM8 channels. Moreover, IGM-18 exerted an analgesic effect on formalin-induced orofacial pain and chronic constriction injury-induced neuropathic pain, demonstrating the involvement of TRPM8 channels in these two pain models. Finally, the results were consistent with TRPM8 downregulation by agonist IGM-5, due to its excessive activation. Conclusions: TRPM8 channels are strongly involved in pain modulation, and their selective antagonist is able to reduce both acute and chronic pain.

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.

Symptom management pathways to reduce ED visits and hospitalizations for patients with cancer.

2018 ◽  
Vol 36 (30_suppl) ◽  
pp. 302-302
Author(s):  
Mohana Roy ◽  
Brian Halbert ◽  
Scott M Devlin ◽  
Jessica A. Zerillo
Keyword(s):  
Chronic Pain ◽  
Symptom Management ◽  
Medical Center ◽  
Treatment Algorithm ◽  
Specific Treatment ◽  
Warning Signs ◽  
Initial Symptom ◽  
Ed Visits ◽  
The Impact ◽  
Management Algorithms

302 Background: At our academic medical center, acute on chronic pain, gastrointestinal symptoms and fever led to most preventable ED visits and hospitalizations amongst cancer patients on chemotherapy. We developed management pathways to target these symptoms. Methods: Existing symptom management algorithms and internal expert consensus of multidisciplinary stakeholders, including palliative care and infectious disease, contributed to initial symptom management algorithms. After iterative revisions, the pathways were finalized by hematology/oncology physician and nursing leadership. We identified outpatient, non-oral, cancer directed treatment events using pharmacy billing data. These events included traditional chemotherapy, immunotherapy, and hormonal therapy. We then identified any ED visit or hospitalization at our medical center within 30 days of the event. We plan a pre-post analysis to determine change in 30-day ED visits and hospitalizations for any reason and for our target symptoms. Results: We developed pathways for acute on chronic pain, nausea/vomiting, diarrhea, constipation, and fever. Each pathway follows a standardized model including warning signs with guidance on direct referral to the ED or urgent clinic referral, the specific treatment algorithm, and helpful references. The pathways were implemented in May 2018. From January 2016 to February 2018, we identified 28,764 treatment events among 4,197 patients. Patient mean age was 63 years. The most commonly used treatments were fluorouracil, leuprolide, and paclitaxel. Within 30 days, 5.7% had an associated ED visit; 5.0% had any hospitalization. Conclusions: We developed management pathways for common symptoms among patients receiving cancer treatment. Generalizing care for such a heterogeneous population can be challenging and requires significant engagement from a multidisciplinary team. Post-intervention data is forthcoming to assess the impact of the pathways on reducing ED visits and hospitalizations.

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.

Sign in / Sign up

Export Citation Format

Share Document