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Veterinary Journal (London, England :... Jun 2024Thoracolumbar hydrated nucleus pulposus extrusion (TL-HNPE) is an increasingly recognised pathology with a substantial lack of literature describing its features. The...
Thoracolumbar hydrated nucleus pulposus extrusion (TL-HNPE) is an increasingly recognised pathology with a substantial lack of literature describing its features. The aim of this retrospective case-control study was to analyse the clinical and magnetic resonance imaging (MRI) features of dogs with TL-HNPE compared to dogs affected with thoracolumbar intervertebral disc extrusion (TL-IVDE). Data from dogs diagnosed with TL-HNPE and TL-IVDE via MRI at two referral hospitals, were retrospectively collected and compared in terms of clinical signs and MRI features. Cases diagnosed with TL-IVDE were deemed controls. The MRI features of the affected IVD space, herniated IVD material, affected overlying spinal cord and local epaxial musculature were evaluated for each group. Fifty-one cases with TL-HNPE and 105 randomly selected cases of TL-IVDE were included. Several signalment and neurological signs were identified as statistically distinct between groups in univariate analysis. Multivariate analysis identified that dogs affected with TL-HNPE were typically older, less likely to be chondrodystrophic (62.2% vs. 91%), more frequently experiencing a peracute onset (90.2% vs. 61.9%) often attributed to a suspected trauma linked with exercise (37.3% vs. 10.5%), being less frequently progressive (41.2% vs. 86.5%) and with herniated disc material less frequently lateralised (72.6% vs. 89.5%) than cases with TL-IVDE. MRI-identifiable intervertebral disc degeneration was found in every TL-IVDE case but only in 60% of TL-HNPE cases. TL-HNPEs were associated to significantly less spinal cord compression and less hyperalgesia than TL-IVDE.
PubMed: 38906413
DOI: 10.1016/j.tvjl.2024.106178 -
BMJ Case Reports Jun 2024Takayasu arteritis is an inflammatory disease of unknown aetiology affecting large vessels. Medium vessel involvement is also well documented; however, neuropathy as a...
Takayasu arteritis is an inflammatory disease of unknown aetiology affecting large vessels. Medium vessel involvement is also well documented; however, neuropathy as a presenting manifestation is rare. In this case report, a young woman in her 20s presented with an 8-month history of intermittent claudication in the right upper limb progressing to rest pain with allodynia in C5-C8 distribution and painless right axillary mass. On examination, she had absent pulses in the right radial, brachial and subclavian artery with audible bruit in the right subclavian and abdominal aorta. CT angiogram showed features suggestive of Takayasu arteritis with a partially thrombosed aneurysm arising from the right axillary artery leading to compression of the right brachial plexus. This patient received treatment with methotrexate and oral corticosteroids. At 3 months follow-up, there was a reduction in the size of the aneurysm, resolution of compressive symptoms and normalisation of inflammatory markers.
Topics: Humans; Takayasu Arteritis; Female; Axillary Artery; Aneurysm; Brachial Plexus Neuropathies; Adult; Computed Tomography Angiography; Methotrexate
PubMed: 38901855
DOI: 10.1136/bcr-2024-260086 -
Redox Biology Jun 2024Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and...
Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and hyperalgesia. At present, however, the mechanisms underlying the development of morphine analgesic tolerance are not fully understood. This tolerance is influenced by various opioid receptor and kinase protein modifications, such as phosphorylation and ubiquitination. Here, we established a murine morphine tolerance model to investigate whether and how S-nitrosoglutathione reductase (GSNOR) is involved in morphine tolerance. Repeated administration of morphine resulted in the down-regulation of GSNOR, which increased excessive total protein S-nitrosation in the prefrontal cortex. Knockout or chemical inhibition of GSNOR promoted the development of morphine analgesic tolerance and neuron-specific overexpression of GSNOR alleviated morphine analgesic tolerance. Mechanistically, GSNOR deficiency enhanced S-nitrosation of cellular protein kinase alpha (PKCα) at the Cys78 and Cys132 sites, leading to inhibition of PKCα kinase activity, which ultimately promoted the development of morphine analgesic tolerance. Our study highlighted the significant role of GSNOR as a key regulator of PKCα S-nitrosation and its involvement in morphine analgesic tolerance, thus providing a potential therapeutic target for morphine tolerance.
PubMed: 38901102
DOI: 10.1016/j.redox.2024.103239 -
Pain and Therapy Jun 2024Sodium pentobarbital (SP), a short- to intermediate-acting barbiturate, has limited information in the existing literature. The objectives of this study are to describe...
Effect of Intravenous Sodium Pentobarbital on Pain and Sensory Abnormalities in Patients with Chronic Non-Cancer Pain: Narrative Literature Review, Research Study, and Illustrative Case Reports.
INTRODUCTION
Sodium pentobarbital (SP), a short- to intermediate-acting barbiturate, has limited information in the existing literature. The objectives of this study are to describe (a) the effect of intravenous (IV) SP infusion on pain and sensory abnormalities, and (b) its utility in the diagnosis and management of patients with chronic pain.
METHODS
A narrative review of barbiturate applications for chronic pain was followed by a pragmatic study of 176 consecutive patients admitted to an inpatient pain unit (2004-2009). We collected demographic information upon admission, diagnoses retrieved from chart review, and pain ratings and sensory abnormalities at baseline and after blinded infusion of normal saline (NS) followed by SP.
RESULTS
The study group consisted of 83 men and 93 women (mean age 41 ± 11 years); the mean NS dose was 7.8 ± 2.3 (range 2-10 ml), the SP dose was 223.8 ± 88 mg (range 40-420), and the numeric rating scale (NRS) baseline pain score was 6.0 ± 2. The mean reduction in NRS reached both statistical and clinical significance in 150 responders to either NS/SP or SP only. Collectively, we found (a) an extremely high rate of response to IV SP irrespective of the underlying pathology, (b) greater response for pain than for sensory abnormalities (sensory gains or deficits), (c) greater response for sensory gain than for sensory deficit, and (d) greater response for allodynia than for pinprick hyperalgesia. Illustrative case reports are also presented.
DISCUSSION
IV SP infusion is a diagnostic tool that assists in elucidating pain generators and the nature of sensory abnormalities (central vs. peripheral), with effects similar to those of IV sodium amytal. The test cannot be viewed as a tell-all diagnostic modality and must be used in conjunction with clinical judgment, investigations, and psychological reports.
PubMed: 38900409
DOI: 10.1007/s40122-024-00621-6 -
Headache Jun 2024Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine.
OBJECTIVE
Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine.
BACKGROUND
Chronic migraine is a leading cause of disability, with higher rates in females. The role of central nervous system neurons and glia in migraine pathophysiology is not fully elucidated. Preclinical studies have shown abnormal glial activation in the trigeminal nucleus caudalis of male rodents. No current reports have investigated glial activation in both sexes in other important brain regions involved with the nociceptive and emotional processing of pain.
METHODS
The mouse nitroglycerin model of migraine was used, and nitroglycerin (10 mg/kg) or vehicle was administered every other day for 9 days. Prior to injections on days 1, 5, and 9, cephalic allodynia was determined by periorbital von Frey hair testing. Immunofluorescent staining of astrocyte marker, glial fibrillary protein (GFAP), and microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), in male and female trigeminal nucleus caudalis, periaqueductal gray, somatosensory cortex, and nucleus accumbens was completed.
RESULTS
Behavioral testing demonstrated increased cephalic allodynia in nitroglycerin- versus vehicle-treated mice. An increase in the percent area covered by GFAP+ cells in the trigeminal nucleus caudalis and nucleus accumbens, but not the periaqueductal gray or somatosensory cortex, was observed in response to nitroglycerin. No significant differences were observed for Iba1 staining across brain regions. We did not detect significant sex differences in GFAP or Iba1 quantification.
CONCLUSIONS
Immunohistochemical analysis suggests that, at the time point tested, immunoreactivity of GFAP+ astrocytes, but not Iba1+ microglia, changes in response to chronic migraine-associated pain. Additionally, there do not appear to be significant differences between males and females in GFAP+ or Iba1+ cells across the four brain regions analyzed.
PubMed: 38899347
DOI: 10.1111/head.14740 -
Seminars in Oncology Nursing Jun 2024Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not...
OBJECTIVES
Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not effective for 40% of survivors. This study examined the ability of a duloxetine-prazosin combination to prevent the development of allodynia and hyperalgesia in a rat model of oxaliplatin-induced peripheral neuropathy (OPIN).
METHODS
Female (n = 24) and male (n = 41) rats were started on duloxetine (15 mg), prazosin (2 mg), or a duloxetine-prazosin combination one week prior to administration of the chemotherapy drug, oxaliplatin, and continued the duloxetine-prazosin combination for 32 days. Behavioral testing for mechanical allodynia and mechanical hyperalgesia was done with selected von Frey filaments over the course of the study.
RESULTS
Overall percent paw withdrawal for rats that received the duloxetine-prazosin combination was significantly lower in female (p < .001 for both conditions) and male (p = .029 for allodynia; p < .001 for hyperalgesia) than those that received water. No significant posttreatment differences were found for allodynia or hyperalgesia between rats treated with duloxetine and rats that received the duloxetine-prazosin combination in either sex.
CONCLUSIONS
These finding provide preliminary evidence that a duloxetine-prazosin combination can prevent the posttreatment development of allodynia and hyperalgesia in both male and female rats; however, the results suggest that the duloxetine-prazosin combination is no more efficacious than duloxetine alone in preventing chronic OIPN.
IMPLICATIONS FOR NURSING PRACTICE
The profession of nursing is built on clinical practice supported by scientific research. The current study addressed the clinical practice problem of prevention and management of painful OIPN, which is a priority area in oncology nursing.
PubMed: 38897856
DOI: 10.1016/j.soncn.2024.151686 -
European Journal of Pharmacology Jun 2024A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy...
A substantial proportion of diabetic patients suffer a debilitating and persistent pain state, known as peripheral painful neuropathy that necessitates improved therapy or antidote. Purpurin, a natural anthraquinone compound from Rubia tinctorum L., has been reported to possess antidepressant activity in preclinical studies. As antidepressants have been typically used as standard agents against persistent neuropathic pain, this study aimed to probe the effect of purpurin on neuropathic pain associated with streptozotocin-induced type 1 diabetes in male C57BL6J mice. The Hargreaves test and the von Frey test were used to assess the pain-like behaviors, shown as heat hyperalgesia and mechanical allodynia respectively. Chronic treatment of diabetic mice with purpurin not only ameliorated the established symptoms of heat hyperalgesia and mechanical allodynia, but also arrested the development of these pain states given preemptively at low doses. Although purpurin treatment hardly impacted on metabolic disturbance in diabetic mice, it ameliorated exacerbated oxidative stress in pain-associated tissues, improved mitochondrial bioenergetics in dorsal root ganglion neurons and restored nerve conduction velocity in sciatic nerves. Notably, the analgesic actions of purpurin were modified by pharmacologically manipulating redox status and mitochondrial bioenergetics. These findings unveil the analgesic activity of purpurin, an effect that is causally associated with its bioenergetics-enhancing and antioxidant effects, in mice with type 1 diabetes.
PubMed: 38897444
DOI: 10.1016/j.ejphar.2024.176749 -
International Journal of Molecular... May 2024Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor...
Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.
Topics: Animals; Paclitaxel; TRPM Cation Channels; TRPV Cation Channels; Ganglia, Spinal; Rats; Neuralgia; Male; Rats, Sprague-Dawley; Hyperalgesia; Capsaicin; Neurons
PubMed: 38892000
DOI: 10.3390/ijms25115813 -
BMJ Open Jun 2024An endogenous pain modulation profile, reflecting antinociceptive and pronociceptive mechanisms, may help to direct management by targeting the involved pain mechanism....
BACKGROUND
An endogenous pain modulation profile, reflecting antinociceptive and pronociceptive mechanisms, may help to direct management by targeting the involved pain mechanism. For individuals with cervicogenic headache (CeH), the characteristics of such profiles were never investigated. However, the individual nature of experiencing pain demands profiling within a multidimensional framework including psychosocial lifestyle characteristics. The objective of the current protocol is to assess the pain modulation profile, which includes psychosocial lifestyle characteristics among people with CeH.
METHODS AND ANALYSIS
A protocol is described to map pain modulation profiles in people with CeH. A cross-sectional non-randomised experimental design will be used to assess feasibility of mapping these profiles. The pain modulation profile is composed based on results on the Depression, Anxiety, Stress Scale, Pittsburgh Sleep Quality Index, Headache Impact Test and on responses to temporal summation of pain (pinprick), conditioned pain modulation and widespread hyperalgesia (mechanical pressure pain threshold and cuff algometry). Primary analyses will report results relating to outcomes on feasibility. Secondary analyses will involve an analysis of proportions (%) of the different psychosocial lifestyle profiles and pain profiles.
ETHICS AND DISSEMINATION
Ethical approval was granted by the Ethics Committee Research UZ/KU Leuven (Registration number B3222024001434) on 30 May 2024. Results will be published in peer-reviewed journals, at scientific conferences and, through press releases. Protocol V.3. protocol date: 3 June 2024.
Topics: Humans; Post-Traumatic Headache; Feasibility Studies; Cross-Sectional Studies; Pain Measurement; Adult; Pain Threshold; Male; Female; Life Style
PubMed: 38890144
DOI: 10.1136/bmjopen-2023-074743 -
Biomedicine & Pharmacotherapy =... Jun 2024The aim of this study was to determine the anti-hypersensitivity activity of novel non-hallucinogenic compounds derived from iboga alkaloids (i.e., ibogalogs), including...
The aim of this study was to determine the anti-hypersensitivity activity of novel non-hallucinogenic compounds derived from iboga alkaloids (i.e., ibogalogs), including tabernanthalog (TBG), ibogainalog (IBG), and ibogaminalog (DM506), using mouse models of neuropathic (Chronic Constriction Injury; CCI) and visceral pain (dextrane sulfate sodium; DSS). Ibogalogs decreased mechanical hyperalgesia and allodynia induced by CCI in a dose- and timeframe-dependent manner, where IBG showed the longest anti-hyperalgesic activity at a comparatively lower dose, whereas DM506 displayed the quickest response. These compounds also decreased hypersensitivity induced by colitis, where DM506 showed the longest activity. To understand the mechanisms involved in these effects, two approaches were utilized: ibogalogs were challenged with the 5-HT receptor antagonist ketanserin and the pharmacological activity of these compounds was assessed at the respective 5-HT 5-HT, and 5-HT receptor subtypes. The behavioral results clearly demonstrated that ketanserin abolishes the pain-relieving activity of ibogalogs without inducing any effect per se, supporting the concept that 5-HT receptor activation, but not inhibition, is involved in this process. The functional results showed that ibogalogs potently activate the 5-HT and 5-HT receptor subtypes, whereas they behave as inverse agonists (except TBG) at the 5-HT receptor. Considering previous studies showing that 5-HT receptor inhibition, but not activation, and 5-HT receptor activation, but not inhibition, relieved chronic pain, we can discard these two receptor subtypes as participating in the pain-relieving activity of ibogalogs. The potential involvement of 5-HT receptor subtypes was also ruled out. In conclusion, the anti-hypersensitivity activity of ibogalogs in mice is mediated by a mechanism involving 5-HT receptor activation.
PubMed: 38889634
DOI: 10.1016/j.biopha.2024.116867