Effects of botulinum toxin A on endometriosis-associated pain and its related mechanism
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ABSTRACT:
SUBMITTER: Tian F
PROVIDER: S-EPMC7533527 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain.MethodsA retrospective, electronic record-based cohort study of StrainprintTM users with self-reported endometriosis was conducted. Self-rated cannabis efficacy, defined as a function of initial and final symptom ratings, was investigated across the included symptom clusters of cramps, pelvic pain, gastrointestinal pain, nausea, depression, and low libido. Cannabis dosage form, dose and cannabinoid ratio information was also recorded.ResultsA total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion.ConclusionsCannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required.
| S-EPMC8547625 | biostudies-literature
Project description:IntroductionTo examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular pain.MethodsTwelve subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: (1) chronic ocular pain; (2) presence of ocular pain over 1 week recall; and (3) presence of photophobia. All individuals underwent an ocular surface examination to capture tear parameters before and 4-6 weeks after BoNT-A injections. Using an event-related fMRI design, subjects were presented with light stimuli during two fMRI scans, once before and 4-6 weeks after BoNT-A injection. Light evoked unpleasantness ratings were reported by subjects after each scan. Whole brain blood oxygen level dependent (BOLD) responses to light stimuli were analyzed.ResultsAt baseline, all subjects reported unpleasantness with light stimulation (average: 70.8 ± 32.0). Four to six weeks after BoNT-A injection, unpleasantness scores decreased (48.1 ± 33.6), but the change was not significant. On an individual level, 50% of subjects had decreased unpleasantness ratings in response to light stimulation compared to baseline ("responders," n = 6), while 50% had equivalent (n = 3) or increased (n = 3) unpleasantness ("non-responders"). At baseline, several differences were noted between responders and non-responders; responders had higher baseline unpleasantness ratings to light, higher symptoms of depression, and more frequent use of antidepressants and anxiolytics, compared to non-responders. Group analysis at baseline displayed light-evoked BOLD responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, midcingulate cortex (MCC), bilateral frontal pole, bilateral cerebellar hemispheric lobule VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, S2 cortices, cerebellar hemispheric lobule VI, cerebellar crus I, and left cerebellar crus II. BoNT-A responders displayed activation of the spinal trigeminal nucleus at baseline where non-responders did not.DiscussionBoNT-A injections modulate light-evoked activation of pain-related brain systems and photophobia symptoms in some individuals with chronic ocular pain. These effects are associated with decreased activation in areas responsible for processing the sensory-discriminative, affective, dimensions, and motor responses to pain.
| S-EPMC10315909 | biostudies-literature
Project description:Objective: To test if botulinum toxin-A (BoNT-A) is effective in reducing chronic muscle-related pain in adults with spastic cerebral palsy (CP), as compared to placebo. Design: A single-center, double-blind, parallel, randomized placebo-controlled trial. The design included an interim analysis to allow for confirmatory analysis, as well as pilot study outcomes. Setting: Tertiary university hospital. Participants: Adults with spastic CP and chronic pain associated with spastic muscle(s). Intervention: Treatment was one session of electromyographically guided intramuscular injections of either BoNT-A or placebo normosaline. Main Study Outcomes: The primary outcome was the proportion who achieved a reduction of pain intensity of two or more steps on the Numerical Rating Scale 6 weeks after treatment. Results: Fifty individuals were screened for eligibility, of whom 16 were included (10 female, 6 male, mean age = 32 years, SD = 13.3 years). The randomization yielded eight participants per treatment arm, and all completed the study as randomized. The study was stopped at the interim analysis due to a low probability, under a preset threshold, of a positive primary outcome. Four individuals were treatment responders in the BoNT-A group for the primary outcome compared to five responders in the placebo group (p = 1.000). Adverse events were mild to moderate. In exploratory analysis, the BoNT-A group had a trend of continuing reduction of pain at the last follow-up, after the primary endpoint. Conclusions: This study did not find evidence that BoNT-A was superior to placebo at the desired effect size (number needed to treat of 2.5) at 6 weeks after treatment. Trial registration:ClinicalTrials.gov: NCT02434549.
| S-EPMC8415259 | biostudies-literature
Project description:Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment. Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and development. Here we evaluate the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) in a mouse model of surgically-induced endometriosis. In this model, female mice develop mechanical hypersensitivity in the caudal abdomen, mild anxiety-like behavior and substantial memory deficits associated with the presence of extrauterine endometrial cysts. Interestingly, daily treatments with THC (2 mg/kg) alleviate mechanical hypersensitivity and pain unpleasantness, modify uterine innervation and restore cognitive function without altering the anxiogenic phenotype. Strikingly, THC also inhibits the development of endometrial cysts. These data highlight the interest of scheduled clinical trials designed to investigate possible benefits of THC for women with endometriosis.
| S-EPMC6977967 | biostudies-literature
Project description:Complex regional pain syndrome is a refractory pain condition with few tested therapies. We hypothesized that botulinum toxin A (BTA) would prolong analgesia after sympathetic blocks in patients with complex regional pain syndrome. We compared the duration of standard lumbar sympathetic block (LSB) with bupivacaine to LSB with bupivacaine and BTA in nine patients with refractory complex regional pain syndrome. Median time to analgesic failure was 71 (95% confidence interval, 12-253) days after LSB with BTA compared with fewer than 10 days (95% confidence interval, 0-12) after standard LSB (log-rank, p < 0.02). BTA profoundly prolonged the analgesia from sympathetic block in this preliminary study.
| S-EPMC2763598 | biostudies-literature
Project description:Diabetes mellitus (DM) is an independent risk factor for overactive bladder (OAB). The pathophysiology of DM-associated OAB is multifactorial and time-dependent. Diabetic bladder dysfunction is highly associated with diabetic complications, mainly including diabetic neuropathy and atherosclerosis. Chronic systemic inflammation and bladder urothelial inflammation may contribute to the onset of OAB. Intravesical botulinum toxin A (BoNT-A) injection has proved to be a successful treatment for idiopathic and neurogenic OAB. BoNT-A can inhibit the efferent pathways of the bladder as well as the chronic inflammation and hypersensitivity via the afferent pathways. We conducted a review of the published literature in Pubmed using a combination of two keywords, namely "botulinum toxin A" (BoNT-A) and "overactive bladder", with or without the additional keywords "detrusor overactivity", "diabetes mellitus", "inflammation", and "urodynamic study". We also reviewed the experience of our research teams, who have published several studies of the association between DM and OAB. Since limited data support the effectiveness and safety of BoNT-A for treating patients with DM-associated OAB, a comprehensive evaluation of diabetic complications and urodynamic study is needed before treatment. In the future, it is imperative to explore the clinical characteristics and inflammatory biomarkers of diabetes as determining predictors of the treatment efficacy.
| S-EPMC7150832 | biostudies-literature
Project description:BackgroundThe mechanism of peripheral axon transport in neuropathic pain is still unclear. Chemokine ligand 13 (CXCL13) and its receptor (C-X-C chemokine receptor type 5, CXCR5) as well as GABA transporter 1 (GAT-1) play an important role in the development of pain. The aim of this study was to explore the axonal transport of CXCL13/CXCR5 and GAT-1 with the aid of the analgesic effect of botulinum toxin type A (BTX-A) in rats.MethodsChronic constriction injury (CCI) rat models were established. BTX-A was administered to rats through subcutaneous injection in the hind paw. The pain behaviors in CCI rats were measured by paw withdrawal threshold and paw withdrawal latencies. The levels of CXCL13/CXCR5 and GAT-1 were measured by western blots.ResultsThe subcutaneous injection of BTX-A relieved the mechanical allodynia and heat hyperalgesia induced by CCI surgery and reversed the overexpression of CXCL13/CXCR5 and GAT-1 in the spinal cord, dorsal root ganglia (DRG), sciatic nerve, and plantar skin in CCI rats. After 10 mmol/L colchicine blocked the axon transport of sciatic nerve, the inhibitory effect of BTX-A disappeared, and the levels of CXCL13/CXCR5 and GAT-1 in the spinal cord and DRG were reduced in CCI rats.ConclusionsBTX-A regulated the levels of CXCL13/CXCR5 and GAT-1 in the spine and DRG through axonal transport. Chemokines (such as CXCL13) may be transported from the injury site to the spine or DRG through axonal transport. Axon molecular transport may be a target to enhance pain management in neuropathic pain.
| S-EPMC9530680 | biostudies-literature
Project description:(1) Background: In dystonia, the somatosensory temporal discrimination threshold (STDT) is abnormally increased at rest and higher and longer-lasting during movement execution in comparison with healthy subjects (HS), suggesting an abnormal sensorimotor integration. These abnormalities are thought to depend on abnormal proprioceptive input coming from dystonic muscles. Since Botulinum toxin-A (BT-A) reduces proprioceptive input in the injected muscles, our study investigated the effects of BT-A on STDT tested at rest and during voluntary movement execution in patients with focal dystonia. (2) Methods: We enrolled 35 patients with focal dystonia: 14 patients with cervical dystonia (CD), 11 patients with blepharospasm (BSP), and 10 patients with focal hand dystonia (FHD); and 12 age-matched HS. STDT tested by delivering paired stimuli was measured in all subjects at rest and during index finger abductions. (3) Results: Patients with dystonia had higher STDT values at rest and during movement execution than HS. While BT-A did not modify STDT at rest, it reduced the abnormal values of STDT during movement in CD and FHD patients, but not in BSP patients. (4) Conclusions: BT-A improved abnormal sensorimotor integration in CD and FHD, most likely by decreasing the overflow of proprioceptive signaling from muscle dystonic activity to the thalamus.
| S-EPMC7290883 | biostudies-literature
Project description:Endometriosis is an estrogen-dependent gynecological disease, with an associated chronic inflammatory component, characterized by the presence of endometrial tissue outside the uterine cavity. Its predominant symptom is pain, a condition notably altering the quality of life of women with the disease. This review is intended to exhaustively gather current knowledge on purinergic signaling in endometriosis-associated pain. Altered extracellular ATP hydrolysis, due to changes in ectonucleotidase activity, has been reported in endometriosis; the resulting accumulation of ATP in the endometriotic microenvironment points to sustained activation of nucleotide receptors (P2 receptors) capable of generating a persistent pain message. P2X3 receptor, expressed in sensory neurons, mediates nociceptive, neuropathic, and inflammatory pain, and is enrolled in endometriosis-related pain. Pharmacological inhibition of P2X3 receptor is under evaluation as a pain relief treatment for women with endometriosis. The role of other ATP receptors is also discussed here, e.g., P2X4 and P2X7 receptors, which are involved in inflammatory cell-nerve and microglia-nerve crosstalk, and therefore in inflammatory and neuropathic pain. Adenosine receptors (P1 receptors), by contrast, mainly play antinociceptive and anti-inflammatory roles. Purinome-targeted drugs, including nucleotide receptors and metabolizing enzymes, are potential non-hormonal therapeutic tools for the pharmacological management of endometriosis-related pain.
| S-EPMC7697899 | biostudies-literature
Project description:Structurally, botulinum toxin type A (BTX-A) is composed of neurotoxin and nontoxic complexing proteins (CPs), and the neurotoxin has the function of blocking acetylcholine release from the neuromuscular junction and therefore paralyzing muscles. Nowadays, a novel botulinum toxin A free of CPs (chinbotulinumtoxin A, A/Chin) is produced, and the present study comprehensively evaluated the dynamic paralytic effect of A/Chin on the gastrocnemius muscle of rats. Different doses (0.01, 0.1, 0.5, 1, 2, and 4 U) of A/Chin and other BTX-As with and without CPs were administered to the gastrocnemius muscles of rats and muscle strength was measured and compared at different postinjection timepoints (from day 0 to 84). With the dose increased, time-to-peak paralytic effect of other BTX-As varied from day 3 to day 14, while A/Chin groups showed rapid and steady time to peak on day 3. At the lowest dose of 0.01 U, A/Chin showed significantly better peak paralytic effect than the others on day 3. When the dose increased to 0.5 U and more, A/Chin group also showed significant paralytic effect when the paralytic effect of other BTX-As was worn off. Moreover, the paralytic effect of A/Chin was confirmed as muscle atrophy while hematoxylin-eosin staining was performed. In conclusion, compared with other BTX-As, A/Chin showed rapid and steady time-to-peak paralytic effect and long-term paralytic efficacy at the same dose level. And it might lay a solid foundation for further wide application of A/Chin in both clinical and cosmetic areas.
| S-EPMC9051373 | biostudies-literature