scholarly journals Peripheral administration of selective GlyT2 inhibitor, oleoyl-D-lysine, is analgesic in neuropathic but not acute or inflammatory pain models in mice

2021 ◽  
Author(s):  
Bruce Wilson ◽  
Julian Peiser-Oliver ◽  
Alexander Gillis ◽  
Sally Evans ◽  
Claudia Alamein ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Respiratory Depression ◽  
Side Effect ◽  
Inflammatory Pain ◽  
Rating Scale ◽  
Lethal Dose ◽  
Whole Body ◽  
Rating Score ◽  
Numerical Rating

Background and Purpose: Changes to spinal glycinergic signalling are a feature of pain chronification. Normalising those changes by inhibiting glycine transporter-2 (GlyT2) is a promising treatment strategy. However, existing GlyT2 inhibitors e.g. ORG25543 are limited by narrow therapeutic windows and severe dose-limiting side effects such as convulsions, and are therefore poor candidates for clinical development. Experimental Approach: Analgesic and side-effect properties of intraperitoneally administered oleoyl-D-lysine, a lipid-based GlyT2 inhibitor, were characterised in mice. Analgesia was assessed in models of chronic neuropathic and inflammatory pain via the von Frey test, and acute nociception via hotplate. Side effects were scored via numerical rating scale, convulsions score, the Rotarod test and whole-body plethysmography for respiratory depression. Key Results: Oleoyl-D-lysine produced significant analgesia/anti-allodynia in the model for chronic neuropathic pain but not for chronic inflammatory or acute pain. No side effects were seen at the peak analgesic dose, 30 mg kg-1. Mild side effects were observed at the highest dose, 100 mg kg-1, in the numerical rating score, but no convulsions. These results contrasted markedly with ORG25543, which produced significant analgesia only at the lethal or near-lethal dose of 50 mg kg-1. At this dose, ORG25543 caused severe side effects on the numerical rating score, severe convulsions, and Rotarod impairment. Oleoyl-D-lysine (30 mg kg-1) did not cause any respiratory depression, a problematic side effect of opiates. Conclusions and Implications: Oleoyl-D-lysine safely and effectively reverses neuropathic pain in mice. GlyT2 inhibitors may be better suited to treating pain of neuropathic origin over other pain aetiologies.

scholarly journals Differential response to scrambler therapy by neuropathic pain phenotypes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Young Gi Min ◽  
Hyun Seok Baek ◽  
Kyoung-Min Lee ◽  
Yoon-Ho Hong
Keyword(s):  
Neuropathic Pain ◽  
Treatment Outcome ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Brief Pain Inventory ◽  
Differential Response ◽  
Open Label ◽  
Numerical Rating ◽  
Scrambler Therapy ◽  
Post Hoc

AbstractScrambler therapy is a noninvasive electroanalgesia technique designed to remodulate the pain system. Despite growing evidence of its efficacy in patients with neuropathic pain, little is known about the clinical factors associated with treatment outcome. We conducted a prospective, open-label, single-arm trial to assess the efficacy and safety of scrambler therapy in patients with chronic neuropathic pain of various etiologies. A post-hoc analysis was performed to investigate whether cluster analysis of the Neuropathic Pain Symptom Inventory (NPSI) profiles could identify a subgroup of patients regarding neuropathic pain phenotype and treatment outcome. Scrambler therapy resulted in a significant decrease in the pain numerical rating scale (NRS) score over 2 weeks of treatment (least squares mean of percentage change from baseline, − 15%; 95% CI − 28% to − 2.4%; p < 0.001). The mean score of Brief Pain Inventory (BPI) interference subdimension was also significantly improved (p = 0.022), while the BPI pain composite score was not. Hierarchical clustering based on the NPSI profiles partitioned the patients into 3 clusters with distinct neuropathic pain phenotypes. Linear mixed-effects model analyses revealed differential response to scrambler therapy across clusters (p = 0.003, pain NRS; p = 0.072, BPI interference subdimension). Treatment response to scrambler therapy appears different depending on the neuropathic pain phenotypes, with more favorable outcomes in patients with preferentially paroxysmal pain rather than persistent pain. Further studies are warranted to confirm that capturing neuropathic pain phenotypes can optimize the use of scrambler therapy.

scholarly journals Clinical Efficacy of Scalene Injection for Thoracic Outlet Syndrome

2021 ◽  
Author(s):  
Samuel Baek ◽  
Seok Kim ◽  
Myung Ho Shin ◽  
Tae Min Kim ◽  
Seoung-Joon Lee ◽  
...  
Keyword(s):  
Side Effects ◽  
Clinical Efficacy ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Neck Disability Index ◽  
Vital Signs ◽  
Treatment Technique ◽  
The Novel ◽  
Numerical Rating ◽  
Neck Disability

Purpose: We introduce the novel treatment technique, scalene injection, and study its clinical efficacy for diagnosis, treatment, and pain control for patients with thoracic outlet syndrome.Methods: Between November 2001 and October 2018, 266 patients were studied retrospectively. To evaluate the efficacy and sustainability, we checked the numerical rating scale (NRS) for pain relief and neck disability index (NDI) for functional improvements, prior to and 1, 12 weeks after the injection. The safety was evaluated by examining side effects for at least 24 hours from the point of injection.Results: NRS was improved from 7.12 to 3.11 at 1 week, and to 3.05 at 12 weeks (p<0.05). NDI was improved from 15.87 to 6.15 at 1 week, and to 6.19 at 12 weeks (p<0.05). There were two cases of convulsion immediately after the injection and were treated with prompt oxygen supply and sedatives. Transient side effects included two cases of dyspnea and one case of nausea and were resolved within 1 hour after. All five cases showed symptoms of side effects on the day of injection and were resolved within a day. A total of 242 patients (91.0%) experienced immediate declines in NRS and 161 patients experienced persistent declines for more than 12 weeks. However, 24 patients (9.0%) showed no improvement and 20 patients (7.5%) experienced increases in NRS.Conclusion: Scalene injection is also effective as a therapeutic method. However, this study suggests that it must be done with monitoring of vital signs in an operating room for any possible complications and side effects.

Short communication: reliability and validity of the UKU Side Effect Rating Scale for adults with intellectual disabilities

2016 ◽  
Vol 10 (3) ◽  
pp. 166-171 ◽  
Author(s):  
Anne Louise Tveter ◽  
Trine Lise Bakken ◽  
Jan Ivar Røssberg ◽  
Egon Bech-Pedersen ◽  
Jørgen G. Bramness
Keyword(s):  
Side Effects ◽  
Focus Group ◽  
Intellectual Disabilities ◽  
Side Effect ◽  
Rating Scale ◽  
Reliability And Validity ◽  
Medical Doctor ◽  
Face Validity ◽  
Content Type ◽  
Adults With Intellectual Disabilities

Purpose – The UKU side effect rating scale for adults with intellectual disabilities (UKU-SERS-ID) was developed to detect side effects among patients with intellectual disabilities (ID). The purpose of this paper is to examine the reliability and face validity of the UKU-SERS-ID. Design/methodology/approach – UKU-SERS-ID comprises 35 items. In total, 22 patients with ID were included from two specialized services for adults with ID and comorbid mental illness. All patients were rated on three different occasions by three clinicians; two nurses and one medical doctor. Reliability was estimated with Cohen’s κ. A focus group discussed the face validity of the items comprising the UKU-SERS-ID. Findings – Respectively ten (nurse-nurse scores) and eight (nurse-doctor scores) items were considered difficult to score due to low prevalence of the symptoms. For the other items the reliability was acceptable. Through discussion in a focus group, with the reliability scores in mind, only one of the items of the UKU-SERS-ID was discarded. Practical implications – The authors have developed a feasible side effect instrument for clinical practice. It is easy to score and relevant regarding important side effects. Originality/value – The UKU-SERS-ID seems to be a feasible tool. Further investigations are mandatory in order to gain knowledge about distribution and phenomenology of side effects from psychotropic medication for individuals with ID.

Tropicamide eye drops reduce clozapine-induced hypersalivation: A case report

2016 ◽  
Vol 33 (S1) ◽  
pp. S543-S544 ◽  
Author(s):  
O. Kilic ◽  
H.M. Ozturk ◽  
E. Ata
Keyword(s):  
Case Report ◽  
Side Effects ◽  
Side Effect ◽  
Negative Symptoms ◽  
Rating Scale ◽  
Short Form ◽  
Eye Drops ◽  
Oral Application ◽  
Competing Interest ◽  
Pressure Changes

IntroductionClozapine-induced sialorrhea (CIS) is a common, treatment-limiting and stigmatizing side effect. All systemic agents that are used for hypersalivation may increase clozapine side effects such as blood pressure changes, constipation, or arrythmias. Oral application of topical anti-muscarinic agents may be a low side effect option for treatment of CIS.ObjectiveThe aim of this case report was to propose an off-label treatment of tropicamide drops to CIS and to stimulate further investigation.Case reportA 33-year-old male inpatient with schizophrenia has been on clozapine 800 mg and amisulpride 600 mg/day. His drooling was occasional and severe as drool drips off his chin during the day and night. Wet area over the pillow, visual analog scale (VAS), the short form of health survey (SF-36), UKU side effect rating scale, scale for the assessment of negative symptoms (SANS), scale for the assessment of positive symptoms (SAPS) were applied at baseline and in one-week intervals. Oral application of one drop of tropicamide % 0.5 (5 mg/mL) to left and one drop to right side before going to bed in the first week and two drops to each side were administered subsequently. Informed consent was given by the patient.ResultsNo psychological, neurological, autonomic and other side effects were observed associated with tropicamide. On VAS, the patient rated hypersalivation 5/7 at baseline, 4/7 after one drop each, 3/7 after two drops each.ConclusionsThe reduction of CIS by oral use of tropicamide eye drops is promising and should be explored with randomized controlled trials.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Differential Response to Scrambler Therapy by Neuropathic Pain Phenotypes

2021 ◽  
Author(s):  
Young Gi Min ◽  
Hyun Seok Baek ◽  
Kyoung-Min Lee ◽  
Yoon-Ho Hong
Keyword(s):  
Neuropathic Pain ◽  
Treatment Outcome ◽  
Rating Scale ◽  
Numerical Rating Scale ◽  
Brief Pain Inventory ◽  
Differential Response ◽  
Sensory Profile ◽  
Open Label ◽  
Numerical Rating ◽  
Scrambler Therapy

Abstract Scrambler therapy is a novel noninvasive electroanalgesia technique designed to remodulate the pain system. Despite growing evidence of its efficacy in patients with neuropathic pain, little is known about the clinical factors associated with treatment outcome. We conducted a prospective, open-label, single-arm trial to assess the efficacy and safety of scrambler therapy in patients with chronic neuropathic pain of various etiologies. A post-hoc analysis was performed to investigate whether cluster analysis of the Neuropathic Pain Symptom Inventory profiles could identify a subgroup of patients regarding neuropathic pain phenotype and treatment outcome. Scrambler therapy resulted in a significant decrease in the pain numerical rating scale (NRS) score over 2 weeks of treatment (least squares mean of percentage change from baseline, −15%; 95% CI, −28% to −2.4%; p < 0.001). The mean score of Brief Pain Inventory (BPI) interference subdimension was also significantly improved (p = 0.022), while the BPI pain composite score was not. Hierarchical clustering partitioned the patients into 3 clusters with distinct neuropathic pain phenotypes. Linear mixed-effects model analyses revealed differential response to scrambler therapy across clusters (p = 0.003, pain NRS; p = 0.072, BPI interference subdimension). Treatment response to scrambler therapy appears different depending on the pain-related sensory profile, with more favorable outcomes in patients with preferentially paroxysmal pain rather than persistent pain. Further studies are warranted to confirm that capturing neuropathic pain phenotypes can optimize the use of scrambler therapy.

scholarly journals Intracerebroventricular Pain Treatment with Analgesic Mixtures including Ziconotide for Intractable Pain

2016 ◽  
Vol 6;19 (6;7) ◽  
pp. E905-E915
Author(s):  
Hélène Staquet
Keyword(s):  
Neuropathic Pain ◽  
Side Effects ◽  
Cancer Pain ◽  
Rating Scale ◽  
Pain Treatment ◽  
Third Ventricle ◽  
High Dose ◽  
Intractable Pain ◽  
Intracerebroventricular Infusion ◽  
Intractable Cancer Pain

Intracerebroventricular (ICV) administration of opioids for control of intractable cancer pain has been used since 1982. We present here our experience of intracerebroventricular administration of pain treatments including ziconotide associated with morphine and ropivacaine for patients resistant to a conventional approach, with nociceptive, neuropathic, or mixed pain. These clinical cases were conducted with patients suffering from refractory pain, more than 6/10 on a numerical pain rating scale (NPRS) while on high-dose medical treatment and/ or intolerance with significant side effects from oral medication. The baseline study visit included a physical examination and an assessment of pain intensity on a NPRS. Under general anesthesia, a neuronavigation device was used to place the catheter on the floor of the third ventricle, supported by an endoscope. Then, drugs were injected in the cerebroventricular system, through a pump (external or subcutaneous). The primary objective was to measure pain evaluation with ICV treatment after a complete withdrawal of other medications. Four patients were enrolled: 3 with intractable cancer pain and one with central neuropathic pain. The median NPRS at baseline was 9.5 [8.5; 19]. The mean NPRS after one month was 3.5 [3; 4.5]. Ziconotide was initiated at 0.48 µg/dy and up to a median of 1.2 µg/dy [1.0; 1.56]. The median dose of morphine and ropivacaine used initially was respectively 0.36 mg/dy [0.24; 0.66] up to 0.6 mg/dy [0.45; 4.63] and 1.2 mg/dy [0; 2.4] up to 2.23 mg/dy [1.2; 3.35]. Minor side effects were initially observed but transiently. One psychiatric agitation required discontinuation of ziconotide infusion. For intractable pain, using ziconotide by intracerebroventricular infusion seems safe and efficient, specifically for chronic neoplastic pain of cervicocephalic, thoracic, or diffuse origin and also for pain arising from a central neuropathic mechanism. Key words: Intracerebroventricular infusion, ziconotide, intractable pain, nociceptive and neuropathic pain

Efficacy and side effect profile of olanzapine versus haloperidol for symptoms of delirium in hospitalized patients with advanced cancer: A multicenter, investigator-blinded, randomized, controlled trial (RCT).

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 231-231
Author(s):  
Maurice Van Der Vorst ◽  
Elisabeth C.W. Neefjes ◽  
Manon S.A. Boddaert ◽  
Bertha A.T.T. Verdegaal ◽  
Aart Beeker ◽  
...  
Keyword(s):  
Side Effects ◽  
Advanced Cancer ◽  
Side Effect ◽  
Rating Scale ◽  
Controlled Trial ◽  
Hospitalized Patients ◽  
Phase Iii ◽  
Side Effect Profile ◽  
Advanced Cancer Patients ◽  
Grade 3

231 Background: Delirium is highly prevalent in patients with advanced cancer. Patients experiencing delirium may require pharmacological treatment to reduce distressing symptoms. Atypical antipsychotics, like olanzapine, are potentially safer and more effective than haloperidol, but no phase III RCTs are reported in patients with advanced cancer. Methods: Hospitalized patients with advanced cancer diagnosed with delirium ( DSM-IV-TR criteria) were randomly assigned centrally (1:1) to olanzapine or haloperidol. Dosages were up-titrated. Primary endpoint was delirium resolution rate (DRR), defined as Delirium Rating Scale-Revised-98 (DRS-R-98) total severity score < 15.25 points and ≥ 4.5 points reduction. Secondary endpoints: time to recovery, grade ≥ 3 side effects (Common Terminology Criteria for Adverse Events version 3.0), and distress (Delirium Experience Questionnaire). The study was powered to increase DRR with 25% for olanzapine compared to haloperidol. Results: Between January 2010 and June 2016, 100 of the anticipated 200 patients were enrolled in the study from 6 sites in the Netherlands and randomly assigned to olanzapine (n = 50) or haloperidol (n = 50). Baseline characteristics were well balanced. Interim analysis showed a difference in DRR of -12.2% (95% confidence interval (CI) = -32.0%- 7.4%); 45% for olanzapine (95% CI 31.0-58.8) vs 57% for haloperidol (95% CI 43.3-71.0), P = 0.22).Time to recovery was 4.5 days in the olanzapine arm vs 2.8 days in the haloperidol arm (P = 0.20). There was no difference in grade ≥ 3 side effects between both arms (OR 0.44, 95% CI 0.14-1.40; P = 0.16). Mean level of distress in patients was 2.1 (SD 1.4) for olanzapine vs 2.3 (SD 1.4) for haloperidol (P = 0.80). Formal interim futility analysis indicated a conditional power of 0.086, implying a very low likelihood (8.6%) of reaching the expected DRR superiority rate of 25% for olanzapine. Therefore, the study was prematurely terminated. Conclusions: No difference in efficacy and side effect profile was observed between haloperidol or olanzapine treatment for delirium in patients with advanced cancer. Clinical trial information: NCT01539733.

Postoperative Analgesia Using Epidural Infusions of Fentanyl with Bupivacaine

1995 ◽  
Vol 83 (4) ◽  
pp. 727-737. ◽  
Author(s):  
David A. Scott ◽  
David S. N. Beilby ◽  
Calum McClymont
Keyword(s):  
Side Effects ◽  
Pain Relief ◽  
Epidural Catheter ◽  
Respiratory Depression ◽  
Rating Scale ◽  
Insertion Site ◽  
Sensory Block ◽  
Epidural Fentanyl ◽  
Major Surgery ◽  
High Dependency

Background Epidural fentanyl/bupivacaine infusions often are limited to high dependency units or intensive care units. One thousand fourteen patients receiving epidural fentanyl/bupivacaine infusions for analgesia after major surgery who were managed in the general surgical ward were prospectively surveyed. Methods Patients leaving the recovery room with an epidural catheter in situ were assessed three times a day by acute pain service personnel for quality of pain relief, using a rating scale that accounted for pain on movement. The presence of side effects and complications was assessed. Results Data were collected from February 1990 to May 1993. The average duration of infusion was 3 days. A patient's pain relief was rated as good to excellent on 82.6% of visits. Side effects possibly attributable to fentanyl included sedation (7.4%), pruritus (10.2%), nausea and vomiting (3.1%), and respiratory depression (1.2%). Respiratory depression commonly was associated with sedation and was detected easily on the postsurgical ward, with only four patients requiring naloxone (0.4%). Side effects possibly related to bupivacaine included unpleasant sensory block (2.6%), significant lower limb motor block (3.0%), and hypotension (6.6%). There were two cases of epidural hematoma. Inflammation at the epidural catheter insertion site occurred in 3.8% (38), of which 42% (16) had some cutaneous purulence detected. There were no epidural space infections. Mechanical problems, including dislodgment of the catheter, accounted for 18.7% of infusion discontinuations within the first 72 h. Conclusions Postoperative epidural fentanyl/bupivacaine infusions are effective and can be managed readily in general postsurgical wards with minimal complications provided that appropriate patient observations are performed.

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