scholarly journals Age and Sex Differences in Acute and Osteoarthritis-Like Pain Responses in Rats

2019 ◽  
Vol 75 (8) ◽  
pp. 1465-1472 ◽  
Author(s):  
Jin Y Ro ◽  
Youping Zhang ◽  
Christina Tricou ◽  
Dan Yang ◽  
Joyce T da Silva ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sex Differences ◽  
Knee Joint ◽  
Weight Bearing ◽  
Female Rats ◽  
Peak Reduction ◽  
Chronic Pain Conditions ◽  
The Impact ◽  
Age And Sex ◽  
Pain Responses

Abstract In this study, we investigated age and sex differences in acute and chronic pain in rats. Groups of young (3–6 months) and aged (20–24 months) male and female Fischer 344 rats were used to assess basal thermal and mechanical thresholds, capsaicin-induced acute nocifensive responses and c-Fos expression in the spinal cord, and monoiodoacetate (MIA)-induced knee osteoarthritis (OA)-like pain responses. There was a significant sex, but not age, effect on thermal threshold on the hindpaw and mechanical threshold on the knee joint. No significant age and sex differences in capsaicin-induced nocifensive and c-Fos responses were observed. MIA induced a greater peak reduction of weight-bearing responses in aged males than young rats. Aged females developed the most profound weight-bearing deficit. With knee joint sensitivity as a primary outcome measure, MIA induced more pronounced and longer-lasting hyperalgesia in older rats, with aged female rats showing the worst effect. These data suggest that age may not have significant effect on acute nociceptive processing, but it significantly impacts OA-like pain, making aged rats, especially females, more vulnerable to chronic pain conditions. These preclinical models should provide important tools to investigate basic mechanisms underlying the impact of age and sex in chronic pain conditions.

scholarly journals Vulnerability factors for mephedrone-induced conditioned place preference in rats—the impact of sex differences, social-conditioning and stress

2021 ◽  
Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  
Keyword(s):  
Sex Differences ◽  
Conditioned Place Preference ◽  
Low Dose ◽  
Social Factor ◽  
Place Preference ◽  
Female Rats ◽  
Male Rats ◽  
Social Conditioning ◽  
Male And Female Rats ◽  
The Impact

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

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 Sex Differences in the Renal Vascular Responses of AT1 and Mas Receptors in Two-Kidney-One-Clip Hypertension

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zahra Pezeshki ◽  
Mehdi Nematbakhsh
Keyword(s):  
Sex Differences ◽  
Female Rats ◽  
Receptor Interaction ◽  
Ang Ii ◽  
Male And Female ◽  
Vascular Responses ◽  
Mas Receptor ◽  
Male And Female Rats ◽  
Renal Vascular ◽  
The Impact

Background. The prevalence and severity of hypertension, as well as the activity of the systemic and local renin angiotensin systems (RASs), are gender related, with more symptoms in males than in females. However, the underlying mechanisms are not well understood. In this study, we investigated sex differences in renal vascular responses to angiotensin II (Ang II) administration with and without Ang II type 1 and Mas receptor (AT1R and MasR) antagonists (losartan and A779) in the 2K1C rat model of renovascular hypertension. Methods. Male and female 2K1C rats were divided into 8 experimental groups (4 of each sex) treated with vehicle, losartan, A779, or A779+losartan. Responses of mean arterial pressure (MAP), renal blood flow (RBF), and renal vascular resistance (RVR) to Ang II were determined. Results. In both sexes, the basal MAP, RBF, and RVR were not significantly different between the four groups during the control period. The Ang II administration decreased RBF and increased RVR in a dose-related manner in both sexes pretreated with vehicle or A779 ( P dose < 0.0001 ), but in vehicle pretreated groups, RBF and RVR responses were different between male and female rats ( P group < 0.05 ). AT1R blockade increased RBF and decreased RVR responses to Ang II, and no difference between the sexes was detected. Coblockades of AT1R and MasR receptors increased RBF response to Ang II significantly in males alone but not in females ( P group = 0.04 ). Conclusion. The impact of Ang II on RBF and RVR responses seems to be gender related with a greater effect on males, and this sex difference abolishes by Mas receptor blockade. However, the paradoxical role of dual losartan and A779 may provide the different receptor interaction in RAS between male and female rats.

scholarly journals The Classification of Patients with Chronic Pain: Age and Sex Differences

2001 ◽  
Vol 6 (3) ◽  
pp. 142-151 ◽  
Author(s):  
Andrew J Cook ◽  
Dania C Chastain
Keyword(s):  
Chronic Pain ◽  
Sex Differences ◽  
Perceived Disability ◽  
Pain Disability ◽  
Clinical Presentations ◽  
Chronic Pain Patients ◽  
Pain Duration ◽  
Pain Patients ◽  
Age And Sex

OBJECTIVE: To further develop an empirically based classification system for chronic pain patients through the examination of age and sex differences, and incorporation of pain duration in the grouping algorithm.SUBJECTS: Three hundred seventy-four chronic pain patients (300 aged 13 to 59 years; 74 aged 60 to 89 years) assessed at an outpatient, multidisciplinary pain management centre.METHODS: Patients completed measures of demographic and descriptive information, pain intensity (box rating scale), perceived disability (modified Pain Disability Index) and affective distress (Symptom Checklist-90 Revised) before multidisciplinary treatment. Standardized scores from the assessment measures were entered into a series of hierarchical, multivariate cluster analyses to identify underlying patient subgroups.RESULTS: Age-based patient groupings from prior research were partially replicated. Significant differences in clinical presentations were observed across age and sex groups. Pain duration was found to make an important contribution to the patient groupings. 'Good control' (low pain, disability, distress) and variants of 'chronic pain syndrome' (elevated pain, disability, distress) groupings were identified across all analyses. Two variants of a 'stoic' profile were identified among older patients, with low levels of distress relative to pain and perceived disability. One of these profiles was associated with long pain duration and was found only among males. Several unique clinical profiles were identified for female patients.CONCLUSIONS: There are important age and sex differences in the clinical presentations of chronic pain patients. Some older patients present with unique clinical profiles that may reflect cohort differences, and/or physiological or psychological adjustment processes. There appears to be a greater number of distinct chronic pain presentations among females. Research on the classification of chronic pain patients within homogeneous diagnostic subgroups is needed.

The impact of the Standard American Diet in rats: Effects on behavior, physiology and recovery from inflammatory injury

2017 ◽  
Vol 17 (1) ◽  
pp. 316-324 ◽  
Author(s):  
Stacie K. Totsch ◽  
Tammie L. Quinn ◽  
Larissa J. Strath ◽  
Laura J. McMeekin ◽  
Rita M. Cowell ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Spinal Cord ◽  
Chronic Pain ◽  
Sex Differences ◽  
Inflammatory Mediators ◽  
Poor Quality ◽  
Mineral Density ◽  
Omega 6 ◽  
Quality Diet ◽  
The Impact

AbstractBackground and aimsObesity is a significant health concern in the Western world and the presence of comorbid conditions suggests an interaction. The overlapping distributions of chronic pain populations and obesity suggests that an interaction may exist. Poor quality diet (high carbohydrates, saturated fats, omega-6 polyunsaturated fatty acids) can lead to increased adiposity which can activate immune cells independent of the activating effect of the diet components themselves. This dual action can contribute to chronic inflammation that may alter susceptibility to chronic pain and prolong recovery from injury. However, traditional examinations of diet focus on high-fat diets that often contain a single source of fat, that is not reflective of an American diet. Thus, we examined the impact of a novel human-relevant (high-carbohydrate) American diet on measures of pain and inflammation in rats, as well as the effect on recovery and immune cell activation.MethodsWe developed a novel, human-relevant Standard American Diet (SAD) to better model the kilocalorie levels and nutrient sources in an American population. Male and female rats were fed the SAD over the course of 20 weeks prior to persistent inflammatory pain induction with Complete Freund’s Adjuvant (CFA). Mechanical and thermal sensitivity were measured weekly. Spontaneous pain, open field locomotion and blood glucose levels were measured during diet consumption. Body composition was assessed at 20 weeks. Following full recovery from CFA-induced hypersensitivity, blood was analyzed for inflammatory mediators and spinal cords were immunohistochemically processed for microglial markers.ResultsChronic consumption of the SAD increased fat mass, decreased lean mass and reduce bone mineral density. SAD-fed rats had increased leptin levels and pro-inflammatory cytokines in peripheral blood serum. Following CFA administration, mechanical sensitivity was assessed and recovery was delayed significantly in SAD-fed animals. Sex differences in the impact of the SAD were also observed. The SAD increased body weight and common T-cell related inflammatory mediators in female, but not male, animals. In males, the SAD had a greater effect on bone mineral density and body composition. Long-term consumption of the SAD resulted in elevated microglial staining in the dorsal horn of the spinal cord, but no sex differences were observed.ConclusionsWe demonstrate the negative effects of an American diet on physiology, behavior and recovery from injury. SAD consumption elevated pro-inflammatory mediators and increased microglial activation in the spinal cord. While there were sex differences in weight gain and inflammation, both sexes showed prolonged recovery from injury.ImplicationsThese data suggest that poor quality diet may increase susceptibility to chronic pain due to persistent peripheral and central immune system activation. Furthermore, consumption of a diet that is high in carbohydrates and omega-6 polyunsaturated fatty acid is likely to lead to protracted recovery following trauma or surgical procedures. These data suggest that recovery of a number of patients eating a poor quality diet may be expedited with a change in diet to one that is healthier.

scholarly journals Inherent Sex Differences in the Expression of the Endocannabinoid System within V1M Cortex and PAG of Sprague Dawley Rats

2021 ◽  
Author(s):  
Aidan Levine ◽  
Erika Liktor-Busa ◽  
Austin A Lipinski ◽  
Sarah Couture ◽  
Shreya Balasubramanian ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Pain ◽  
Sex Differences ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Female Population ◽  
Sprague Dawley Rats ◽  
Chronic Pain Conditions

Abstract Background: Several chronic pain disorders, such as migraine and fibromyalgia, have an increased prevalence in the female population. The underlying mechanisms of this sex-biased prevalence have yet to be thoroughly documented but could be related to endogenous differences in neuromodulators in pain networks, including the endocannabinoid system. The cellular endocannabinoid system is comprised of the endogenous lipid signals 2-AG (2-arachidonoylglycerol) and AEA (anandamide); the enzymes that synthesize and degrade them; and the cannabinoid receptors. The relative prevalence of different components of the endocannabinoid system in specific brain regions may alter responses to endogenous and exogenous ligands. Methods: Brain tissue from naïve male and female Sprague Dawley rats was harvested from V1M cortex, periaqueductal gray, trigeminal nerve, and trigeminal nucleus caudalis. Tissue was analyzed for relative levels of endocannabinoid enzymes, ligands, and receptors via mass spectrometry, unbiased proteomic analysis, and immunohistochemistry. Results: Mass spectrometry revealed cortical AEA levels were significantly higher in males compared to females (p<0.001), whereas 2-AG levels in periaqueductal grey were significantly higher in females compared to males (p<0.0001). Immunohistochemistry followed by unbiased proteomics confirmed the prevalence of 2-AG-endocannabinoid system enzymes in the female PAG.Conclusions: Our results suggest that sex differences exist in the endocannabinoid system in two CNS regions relevant to cortical spreading depression (V1M cortex) and descending modulatory networks in pain/anxiety (PAG). These basal differences in endogenous endocannabinoid mechanisms may facilitate the development of chronic pain conditions and may also underlie sex differences in response to therapeutic intervention.

scholarly journals Sex differences in the expression of the endocannabinoid system within V1M cortex and PAG of Sprague Dawley rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aidan Levine ◽  
Erika Liktor-Busa ◽  
Austin A. Lipinski ◽  
Sarah Couture ◽  
Shreya Balasubramanian ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Pain ◽  
Sex Differences ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Female Population ◽  
Sprague Dawley Rats ◽  
Chronic Pain Conditions

Abstract Background Several chronic pain disorders, such as migraine and fibromyalgia, have an increased prevalence in the female population. The underlying mechanisms of this sex-biased prevalence have yet to be thoroughly documented, but could be related to endogenous differences in neuromodulators in pain networks, including the endocannabinoid system. The cellular endocannabinoid system comprises the endogenous lipid signals 2-AG (2-arachidonoylglycerol) and AEA (anandamide); the enzymes that synthesize and degrade them; and the cannabinoid receptors. The relative prevalence of different components of the endocannabinoid system in specific brain regions may alter responses to endogenous and exogenous ligands. Methods Brain tissue from naïve male and estrous staged female Sprague Dawley rats was harvested from V1M cortex, periaqueductal gray, trigeminal nerve, and trigeminal nucleus caudalis. Tissue was analyzed for relative levels of endocannabinoid enzymes, ligands, and receptors via mass spectrometry, unlabeled quantitative proteomic analysis, and immunohistochemistry. Results Mass spectrometry revealed significant differences in 2-AG and AEA concentrations between males and females, as well as between female estrous cycle stages. Specifically, 2-AG concentration was lower within female PAG as compared to male PAG (*p = 0.0077); female 2-AG concentration within the PAG did not demonstrate estrous stage dependence. Immunohistochemistry followed by proteomics confirmed the prevalence of 2-AG-endocannabinoid system enzymes in the female PAG. Conclusions Our results suggest that sex differences exist in the endocannabinoid system in two CNS regions relevant to cortical spreading depression (V1M cortex) and descending modulatory networks in pain/anxiety (PAG). These basal differences in endogenous endocannabinoid mechanisms may facilitate the development of chronic pain conditions and may also underlie sex differences in response to therapeutic intervention.

scholarly journals The Impact of Sampling and Measurement on the Prevalence of Self-Reported Pain in Canada

2003 ◽  
Vol 8 (3) ◽  
pp. 157-163 ◽  
Author(s):  
Elizabeth G Van Den Kerkhof ◽  
Wilma M Hopman ◽  
Tanveer E Towheed ◽  
Tassos P Anastassiades ◽  
David H Goldstein
Keyword(s):  
Chronic Pain ◽  
General Population ◽  
Health Survey ◽  
Public Health Problem ◽  
Short Term ◽  
Canadian Population ◽  
Prevalence Estimates ◽  
Prevalence Of Pain ◽  
The Impact ◽  
Age And Sex

BACKGROUND: Pain is an important public health problem in Canada. International estimates of general population pain prevalence range from 2% to 46%.OBJECTIVES: The purpose of this paper is to critically examine the potentially misleading use of overall prevalence estimates in the pain literature and to use two Canadian population-based surveys to assess the impact of sampling and measurement on prevalence.METHODS: Two of the secondary data sets used were the 1996/97 National Population and Health Survey (NPHS) and the Canadian Multicentre Osteoporosis Study (CaMos). This paper is based on the assessment of chronic pain in the NPHS, and the assessment of short term pain using the Medical Outcomes Trust's 36-item health survey and the Health Utilities Index, both collected by CaMos. Data are presented as frequencies and percentages overall and stratified by age and sex. CaMos prevalence estimates were age and sex-standardized to the NPHS population.RESULTS: The overall prevalence of pain was 39% for one-week pain, 66% for four-week pain and 15% for chronic pain. Women were more likely to report pain than men and the prevalence of pain increased with age.CONCLUSIONS: This study yields useful information about the self-reported responses to a variety of questions assessing pain in the general population. Responses to the different questions likely represent different categories of pain, such as short term versus chronic pain, which in turn may have different epidemiological risk factors and profiles. Longitudinal studies of the epidemiology, predictors and natural history of chronic pain are urgently needed in the Canadian population.

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