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Lasers in Medical Science May 2024The purpose of this study is to explore the potential application of photobiomodulation to irritable bowel syndrome. We established the following experimental groups:...
The purpose of this study is to explore the potential application of photobiomodulation to irritable bowel syndrome. We established the following experimental groups: the Non-Stress + Sham group, which consisted of rats that were not restrained and were only subjected to sham irradiation; the Stress + Sham group, which underwent 1 hour of restraint stress followed by sham irradiation; and the Stress + Laser group, which was subjected to restraint stress and percutaneous laser irradiation bilaterally on the L6 dorsal root ganglia for 5 minutes each. The experiment was conducted twice, with three and two laser conditions examined. Following laser irradiation, a barostat catheter was inserted into the rat's colon. After a 30-minute acclimatization period, the catheter was inflated to a pressure of 60 mmHg, and the number of abdominal muscle contractions was measured over a 5-minute period. The results showed that photobiomodulation significantly suppressed the number of abdominal muscle contractions at average powers of 460, 70, and 18 mW. However, no significant suppression was observed at average powers of 1 W and 3.5 mW. This study suggests that photobiomodulation can alleviate visceral hyperalgesia induced by restraint stress, indicating its potential applicability to irritable bowel syndrome.
Topics: Animals; Low-Level Light Therapy; Rats; Hyperalgesia; Male; Restraint, Physical; Irritable Bowel Syndrome; Rats, Sprague-Dawley; Stress, Psychological; Muscle Contraction; Abdominal Muscles; Disease Models, Animal
PubMed: 38806837
DOI: 10.1007/s10103-024-04091-2 -
Cureus Apr 2024Pain management in patients on chronic opioid therapy is a common clinical challenge. The phenomena of opioid-induced hyperalgesia and tolerance are important...
Pain management in patients on chronic opioid therapy is a common clinical challenge. The phenomena of opioid-induced hyperalgesia and tolerance are important contributors to that challenge. There are multiple strategies described to wean opioid doses and/or transition patients off opioids altogether. However, there is very little data to guide transitions off chronic intrathecal opioids. Here, we report on two patients with intractable post-laminectomy pain syndrome, resulting in severe functional limitation in the setting of opioid escalation culminating in the intrathecal delivery of hydromorphone to daily doses as high as 20 mg/day. We describe their rapid successful weaning off opioids using low-dose buprenorphine, which resulted in a dramatic improvement in pain and function.
PubMed: 38803786
DOI: 10.7759/cureus.59134 -
Experimental and Molecular Pathology Jun 2024pathological pain and Attention-deficit/hyperactivity disorder (ADHD) are two complex multifactorial syndromes. The comorbidity of ADHD and altered pain perception is...
pathological pain and Attention-deficit/hyperactivity disorder (ADHD) are two complex multifactorial syndromes. The comorbidity of ADHD and altered pain perception is well documented in children, adolescents, and adults. According to pathophysiological investigations, the dopaminergic system's dysfunction provides a common basis for ADHD and comorbid pain. Growing evidence suggests that oxidative stress may be crucial in both pathologies. Recent studies revealed that a small peptide encompassing the redox-active site of selenoprotein T (PSELT), protects dopaminergic neurons and fibers as well as lesioned nerves in animal models. The current study aims to examine the effects of PSELT treatment on ADHD-like symptoms and pain sensitivity, as well as the role of catecholaminergic systems in these effects. Our results demonstrated that intranasal administration of PSELT reduced the hyperactivity in the open field, decreased the impulsivity displayed by 6-OHDA-lesioned male mice in the 5-choice serial reaction time task test and improved attentional performance. In addition, PSELT treatment significantly increased the nociception threshold in both normal and inflammatory conditions. Furthermore, anti-hyperalgesic activity was antagonized with sulpiride pre-treatment, but not by phentolamine, or propranolol pre-treatments. The present study suggests that PSELT reduces the severity of ADHD symptoms in mice and possesses potent antinociceptive effects which could be related to the involvement of D2/D3 dopaminergic receptors.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Oxidopamine; Mice; Male; Pain; Disease Models, Animal; Hyperalgesia; Animals, Newborn; Selenoproteins; Sulpiride
PubMed: 38797131
DOI: 10.1016/j.yexmp.2024.104905 -
European Journal of Paediatric... May 2024We investigated differences in somatosensory profiles (SSPs) assessed by quantitative sensory testing in children and adolescents with cerebral palsy (CCP) with and...
OBJECTIVE
We investigated differences in somatosensory profiles (SSPs) assessed by quantitative sensory testing in children and adolescents with cerebral palsy (CCP) with and without chronic pain and compared these differences to those in a group of typically developed children and adolescents (TDC) with and without chronic pain.
METHOD
All included subjects were consecutively recruited from and tested at the same outpatient orthopedic clinic by the same investigator. The subjects had their reaction times tested. The SSP consisted of the following tests: warmth (WDT), cool (CDT), mechanical (MDT), and vibration (VDT) detection thresholds; heat (HPT), pressure (PPT), and mechanical (MPT) pain thresholds; wind-up ratio (WUR); dynamic mechanical allodynia (DMA) and cold pressor test (CPT) using a conditioned pain modulation (CPM) paradigm.
RESULTS
We included 25 CCP and 26 TDC. TDC without chronic pain served as controls. In TDC with chronic pain, WDT, HPT, HPT intensity, and PPT were higher than in controls. No differences in SSPs between CCP with and without chronic pain were observed. In CCP, the MDT, WDT, CDT, and HPT intensity were higher than in controls. CCP had longer reaction times than TDC. There were no differences regarding the remaining variables.
DISCUSSION
In CCP, the SSPs were independent of pain status and findings on MR images. In all CCP the SSPs resembled TDC with chronic pain, compared to TDC without chronic pain. This suggests that CCP do not have the normal neuroplastic adaptive processes that activate and elicit functional changes in the central and peripheral nervous systems.
PubMed: 38795436
DOI: 10.1016/j.ejpn.2024.05.007 -
Pharmaceuticals (Basel, Switzerland) May 2024Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative...
Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.
PubMed: 38794204
DOI: 10.3390/ph17050633 -
Pharmaceuticals (Basel, Switzerland) Apr 2024Species of the genus are used in popular medicine for pain, inflammatory symptoms, and mental disorders. (Müll. Arg.) Standl. (Rubiaceae) is commonly known as coffee...
A Comprehensive Description of the Anatomy and Histochemistry of (Müll. Arg.) Standl. and an Investigation into Its Anti-Inflammatory Effects in Mice and Role in Scopolamine-Induced Memory Impairment.
Species of the genus are used in popular medicine for pain, inflammatory symptoms, and mental disorders. (Müll. Arg.) Standl. (Rubiaceae) is commonly known as coffee and some scientific studies have demonstrated its therapeutic potential. The goal of this study was to investigate the anti-inflammatory and neuroprotective effects, and acetylcholinesterase (AChE) inhibitory activity of a methanolic extract obtained from leaves of (MEPC), as well as the micromorphology and histochemistry of the leaves and stems of this plant. In addition, the MEPC was analyzed by UHPLC-MS/MS and the alkaloidal fraction (AF) obtained from the MEPC was tested in a mouse model of inflammation. MEPC contained three indole alkaloids, one sesquiterpene (megastigmane-type) and two terpene lactones. MEPC (3, 30 and 100 mg/kg) and AF (3 and 30 mg/kg) were evaluated in inflammation models and significantly inhibited edema at 2 h and 4 h, mechanical hyperalgesia after 4 h and the response to cold 3 h and 4 h after carrageenan injection. Scopolamine significantly increased the escape latency, and reduced the swimming time and number of crossings in the target quadrant and distance, while MEPC (3, 30 and 100 mg/kg), due to its neuroprotective actions, reversed these effects. AChE activity was significantly decreased in the cerebral cortex (52 ± 3%) and hippocampus (60 ± 3%), after MEPC administration. Moreover, micromorphological and histochemical information was presented, to aid in species identification and quality control of . The results of this study demonstrated that is an anti-inflammatory and antihyperalgesic agent that can treat acute disease and enhance memory functions in mouse models.
PubMed: 38794135
DOI: 10.3390/ph17050564 -
Cancers May 2024Bone cancer and its related chronic pain are huge clinical problems since the available drugs are often ineffective or cannot be used long term due to a broad range of...
Osteosarcoma-Induced Pain Is Mediated by Glial Cell Activation in the Spinal Dorsal Horn, but Not Capsaicin-Sensitive Nociceptive Neurons: A Complex Functional and Morphological Characterization in Mice.
Bone cancer and its related chronic pain are huge clinical problems since the available drugs are often ineffective or cannot be used long term due to a broad range of side effects. The mechanisms, mediators and targets need to be identified to determine potential novel therapies. Here, we characterize a mouse bone cancer model induced by intratibial injection of K7M2 osteosarcoma cells using an integrative approach and investigate the role of capsaicin-sensitive peptidergic sensory nerves. The mechanical pain threshold was assessed by dynamic plantar aesthesiometry, limb loading by dynamic weight bearing, spontaneous pain-related behaviors via observation, knee diameter with a digital caliper, and structural changes by micro-CT and glia cell activation by immunohistochemistry in BALB/c mice of both sexes. Capsaicin-sensitive peptidergic sensory neurons were defunctionalized by systemic pretreatment with a high dose of the transient receptor potential vanilloid 1 (TRPV1) agonist resiniferatoxin (RTX). During the 14- and 28-day experiments, weight bearing on the affected limb and the paw mechanonociceptive thresholds significantly decreased, demonstrating secondary mechanical hyperalgesia. Signs of spontaneous pain and osteoplastic bone remodeling were detected both in male and female mice without any sex differences. Microglia activation was shown by the increased ionized calcium-binding adapter molecule 1 (Iba1) immunopositivity on day 14 and astrocyte activation by the enhanced glial fibrillary acidic protein (GFAP)-positive cell density on day 28 in the ipsilateral spinal dorsal horn. Interestingly, defunctionalization of the capsaicin-sensitive afferents representing approximately 2/3 of the nociceptive fibers did not alter any functional parameters. Here, we provide the first complex functional and morphological characterization of the K7M2 mouse osteosarcoma model. Bone-cancer-related chronic pain and hyperalgesia are likely to be mediated by central sensitization involving neuroinflammation via glial cell activation in the spinal dorsal horn, but not the capsaicin-sensitive sensory neuronal system.
PubMed: 38791867
DOI: 10.3390/cancers16101788 -
Cells May 2024The inhibition of endocannabinoid hydrolysis by enzymatic inhibitors may interfere with mechanisms underlying migraine-related pain. The dual FAAH/MAGL inhibitor AKU-005...
The inhibition of endocannabinoid hydrolysis by enzymatic inhibitors may interfere with mechanisms underlying migraine-related pain. The dual FAAH/MAGL inhibitor AKU-005 shows potent inhibitory activity in vitro. Here, we assessed the effect of AKU-005 in a migraine animal model based on nitroglycerin (NTG) administration. Male rats were treated with AKU-005 (0.5 mg/kg, i.p.) or vehicle 3 h after receiving NTG (10 mg/kg, i.p.) or NTG vehicle. One hour later, rats were subjected to the open field test followed by the orofacial formalin test. At the end of the test, we collected serum samples for assessing calcitonin gene-related peptide (CGRP) levels as well as meninges, trigeminal ganglia, and brain areas to assess mRNA levels of CGRP and pro-inflammatory cytokines, and endocannabinoid and related lipid levels. AKU-005 reduced NTG-induced hyperalgesia during the orofacial formalin test but did not influence NTG-induced changes in the open field test. It significantly reduced serum levels of CGRP, CGRP, and pro-inflammatory cytokine mRNA levels in the meninges, trigeminal ganglia, and central areas. Surprisingly, AKU-005 caused no change in endocannabinoids and related lipids in the regions evaluated. The present findings suggest that AKU-005 may have anti-migraine effects by reducing CGRP synthesis and release and the associated inflammatory events. This effect, however, does not seem mediated via an interference with the endocannabinoid pathway.
Topics: Animals; Male; Hyperalgesia; Rats; Amidohydrolases; Calcitonin Gene-Related Peptide; Trigeminal Ganglion; Rats, Sprague-Dawley; Monoacylglycerol Lipases; Endocannabinoids; Nitroglycerin; Disease Models, Animal; Cytokines; Migraine Disorders; Enzyme Inhibitors; Oligopeptides; Salivary Proteins and Peptides
PubMed: 38786051
DOI: 10.3390/cells13100830 -
Journal of Parasitology Research 2024Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive...
Comorbidities that involve infectious and noninfectious diseases, such as malaria and cancer, have been described. Cancer and malaria induce changes in the nociceptive and inflammatory responses through similar pathophysiological mechanisms. However, it is unclear whether malaria and antimalarial treatment can change the inflammatory and nociceptive responses induced by solid cancer. Therefore, the present study experimentally evaluated the effect of infection by strain ANKA and chloroquine treatment on the nociceptive and inflammatory responses induced by the solid Ehrlich tumor in male BALB/c mice. On the 1 experimental day, mice were infected with and injected with tumor cells in the left hind paw. From the 7 to the 9 experimental day, mice were treated daily with chloroquine. The parasitemia was evaluated on the 7 and 10 days after infection. On the 11 experimental day, mice were evaluated on the von Frey filament test, the hot plate test, and the paw volume test. At the end of the experimental tests on the 11th day, the peripheral blood of all mice was collected for dosing of IL-1 and TNF-. The blood parasitemia significantly increased from the 7 to the 10 day. The chloroquine treatment significantly decreased the parasitemia on the 10 day. The presence of the tumor did not significantly change the parasitemia on the 7 and 10 days in mice treated and nontreated with chloroquine. On the 11 day, the mechanical and thermal nociceptive responses significantly increased in mice with tumors. The treatment with antimalarial significantly reduced the mechanical nociceptive response induced by tumors. The hyperalgesia induced by tumors did not change with malaria. The mechanical and thermal hyperalgesia induced by the tumor was significantly reduced in mice treated and healed from malaria. On the 11 day, the volume of the paw injected by the tumor was significantly increased. The mice treated with chloroquine, infected with malaria, or healed of malaria showed reduced paw edema induced by the tumor. Mice with tumors did not show a change in IL- and TNF- serum levels. Mice with tumors showed a significant increase in serum levels of IL-1 but not TNF- when treated with chloroquine, infected with malaria, or healed of malaria. In conclusion, the results show that malaria infection and chloroquine treatment can influence, in synergic form, the nociceptive and inflammatory responses induced by the solid tumor. Moreover, the mechanical antinociception, the thermal hyperalgesia, and the antiedema effect observed in mice treated with chloroquine and healed from malaria can be related to the increase in the serum level of IL-1.
PubMed: 38774541
DOI: 10.1155/2024/3771926 -
Molecular Pain 2024Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of...
Methylene blue (MB) has been shown to reduce mortality and morbidity in vasoplegic patients after cardiac surgery. Though MB is considered to be safe, extravasation of MB leading to cutaneous toxicity has been reported. In this study, we sought to characterize MB-induced cutaneous toxicity and investigate the underlying mechanisms. To induce MB-induced cutaneous toxicity, we injected 64 adult male Sprague-Dawley rates with 200 µL saline (vehicle) or 1%, 0.1%, or 0.01% MB in the plantar hind paws. Paw swelling, skin histologic changes, and heat and mechanical hyperalgesia were measured. Injection of 1%, but not 0.1% or 0.01% MB, produced significant paw swelling compared to saline. Injection of 1% MB produced heat hyperalgesia but not mechanical hyperalgesia. Pain behaviors were unchanged following injections of 0.1% or 0.01% MB. Global transcriptomic analysis by RNAseq identified 117 differentially expressed genes (111 upregulated, 6 downregulated). Ingenuity Pathway Analysis showed an increased quantity of leukocytes, increased lipids, and decreased apoptosis of myeloid cells and phagocytes with activation of IL-1β and Fos as the two major regulatory hubs. qPCR showed a 16-fold increase in IL-6 mRNA. Thus, using a novel rat model of MB-induced cutaneous toxicity, we show that infiltration of 1% MB into cutaneous tissue causes a dose-dependent pro-inflammatory response, highlighting potential roles of IL-6, IL-1β, and Fos. Thus, anesthesiologists should administer dilute MB intravenously through peripheral venous catheters. Higher concentrations of MB (1%) should be administered through a central venous catheter to minimize the risk of cutaneous toxicity.
Topics: Animals; Male; Rats, Sprague-Dawley; Methylene Blue; Hyperalgesia; Inflammation; Disease Models, Animal; Skin; Dose-Response Relationship, Drug; Hot Temperature; Rats; Interleukin-1beta
PubMed: 38773702
DOI: 10.1177/17448069241259535