Influences of Suvorexant and Mirtazapine on Chronic Pain-related Sleep Disorder in Neuropathic Pain Model Mice

Abstract Chronic pain and sleep disorders are independently associated with a reduction in the quality of life. They can be both a cause and consequence of each other; therefore, they should be treated simultaneously. However, optimal treatments for chronic pain-related sleep disorders are not well established. Here, we aimed to investigate the effects of suvorexant, a novel sleep drug, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, on pain-related sleep disorders in a preclinical neuropathic pain mouse model, which was produced by partial sciatic nerve ligation. We calculated the quantity, duration, and depth of sleep by analyzing the electroencephalogram. Voluntary activity was also evaluated by counting the number of wheel rotations with special cages. Daily administration of suvorexant and mirtazapine normalized the reduced rapid eye movement (REM) and non-REM sleep and improved the fragmented sleep, further regaining the depth of sleep at sleep onset in the chronic pain state. Suvorexant decreased voluntary activity, which was prolonged after the end of administration; however, mirtazapine did not decrease it. Both suvorexant and mirtazapine could be potential therapeutic agents for chronic pain-related sleep disorders.

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Efficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain

Regional Anesthesia and Pain Medicine ◽

10.1136/rapm-2018-000013 ◽

2019 ◽

Vol 44 (1) ◽

pp. 111-117 ◽

Cited By ~ 6

Author(s):

Jeffrey S Kroin ◽

Vaskar Das ◽

Mario Moric ◽

Asokumar Buvanendran

Keyword(s):

Chronic Pain ◽

Neuropathic Pain ◽

Postoperative Pain ◽

Mechanical Allodynia ◽

Pain Syndrome ◽

Saline Control ◽

Pain Model ◽

Time Period ◽

Pain Models ◽

Neuropathic Pain Model

Background and objectivesKetamine has been shown to reduce chronic pain; however, the adverse events associated with ketamine makes it challenging for use outside of the perioperative setting. The ketamine metabolite (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) has a therapeutic effect in mice models of depression, with minimal side effects. The objective of this study is to determine if (2R,6R)-HNK has efficacy in both acute and chronic mouse pain models.MethodsMice were tested in three pain models: nerve-injury neuropathic pain, tibia fracture complex regional pain syndrome type-1 (CRPS1) pain, and plantar incision postoperative pain. Once mechanical allodynia had developed, systemic (2R,6R)-HNK or ketamine was administered as a bolus injection and compared with saline control in relieving allodynia.ResultsIn all three models, 10 mg/kg ketamine failed to produce sustained analgesia. In the neuropathic pain model, a single intraperitoneal injection of 10 mg/kg (2R,6R)-HNK elevated von Frey thresholds over a time period of 1–24hours compared with saline (F=121.6, p<0.0001), and three daily (2R,6R)-HNK injections elevated von Frey thresholds for 3 days compared with saline (F=33.4, p=0.0002). In the CRPS1 model, three (2R,6R)-HNK injections elevated von Frey thresholds for 3 days and then an additional 4 days compared with saline (F=116.1, p<0.0001). In the postoperative pain model, three (2R,6R)-HNK injections elevated von Frey thresholds for 3 days and then an additional 5 days compared with saline (F=60.6, p<0.0001).ConclusionsThis study demonstrates that (2R,6R)-HNK is superior to ketamine in reducing mechanical allodynia in acute and chronic pain models and suggests it may be a new non-opioid drug for future therapeutic studies.

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In Vivo Biocompatibility of Alginate-PLL Microcapsules with Chromaffin Cells for the Alleviation of Chronic Pain

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.277-279.62 ◽

2005 ◽

Vol 277-279 ◽

pp. 62-66 ◽

Cited By ~ 1

Author(s):

Yu Mi Kim ◽

Young Hoon Jeon ◽

Gwang Chun Jin ◽

Jeong Ok Lim ◽

Woon Yi Baek

Keyword(s):

Chronic Pain ◽

Neuropathic Pain ◽

Chromaffin Cells ◽

Adrenal Chromaffin Cells ◽

Cold Allodynia ◽

Pain Model ◽

Prominent Symptom ◽

Neuropathic Pain Model ◽

Adrenal Chromaffin

Intrathecal implants of adrenal medullary chromaffin cells relieve chronic pain by secreting catecholamines, opioids and other neuroactive substances. Recently, macrocapsules with hollow fibers were employed to isolate immunologically xenogeneic chromaffin cells, but the poor viability in vivo of the encapsulated chromaffin cells limited the usefulness of this method. In this study, we used microencapsulation technology to increase the viability of chromaffin cells. Bovine adrenal chromaffin cells were microencapsulated with alginate and poly-L-lysine and implanted intrathecally in a rat using the neuropathic pain model. Intrathecal implants of microencapsulated cells relieved cold allodynia, which is the most prominent symptom of the neuropathic pain model in a rat. Furthermore, the microencapsulated chromaffin cells were morphologically normal and retained their functionality. These findings suggest that the intrathecal implant of microencapsulated chromaffin cells might be a useful method for treating chronic pain.

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Anti-Neuropathic Pain Activity of A Cationic Palladium (II) Dithiocarbamate By Suppressing The Inflammatory Mediators in Paclitaxel-Induced Neuropathic Pain Model

10.21203/rs.3.rs-350075/v1 ◽

2021 ◽

Author(s):

Muhammad Naveed ◽

Rahim Ullah ◽

Adnan Khan ◽

Bushra Shal ◽

Ashraf Ullah Khan ◽

...

Keyword(s):

Neuropathic Pain ◽

Neuroprotective Effect ◽

No Production ◽

Pain Model ◽

Novel Drugs ◽

Motor Activities ◽

Neuropathic Pain Model ◽

Pain State ◽

Mrna Gene ◽

Cox 2

Abstract Neuropathic pain is an obstinate chronic pain state which extremely worsens the quality of life of the suffered population. It is still intended as an intractable disease as existing therapies are not excellent in terms of efficacy and tolerability. Therefore, to search for novel drugs are crucial to acquire satisfactory treatments. The present study investigated the possible antiallodynic, antihyperalgesic and neuroprotective activities of (1,4-bis-(diphenylphosphino) butane) palladium (II)chloride monohydrate-(1) in Paclitaxel (PTX)-induced neuropathic pain model (Fig.10). Initially, 1 (5 and 10 mg/kg, b.w) was investigated for antinociceptive activities at behavioral level by performing mechanical and cold allodynia as well as thermal and tail immersion hyperalgesia. RT-PCR was performed to determine the suppressing effect of 1 on mRNA expression level of iNOS, COX-2 and proinflammatory cytokines (TNF-α, IL-1β, IL-6). In addition, antioxidant protein and enzymes (GSH, GST, Catalase), NO, MDA level and muscle activity were also determined. The results demonstrate that once daily dosing of 1 significantly repressed the behavioral pain responses dose dependently. Moreover, the mRNA gene expression of iNOS, COX-2 and inflammatory cytokines were reduced noticeably by 1. Furthermore, the treatment enhanced the level of antioxidant enzymes and lowered the level of MDA and NO production with no effect on motor activities of rats. These findings suggest the potential of 1 to attenuate neuropathic pain, neuroinflammation and neuroprotective effect. Thereupon, 1 might be a dynamic candidate for the therapeutic management of chronic neuropathic pain.

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Faculty Opinions recommendation of Modulation of the anti-nociceptive effects of 2-arachidonoyl glycerol by peripherally administered FAAH and MGL inhibitors in a neuropathic pain model.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1126773.583854 ◽

2008 ◽

Author(s):

Roger Pertwee ◽

Maria Grazia Cascio

Keyword(s):

Neuropathic Pain ◽

Pain Model ◽

Neuropathic Pain Model ◽

Arachidonoyl Glycerol

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The activation of galanin receptor 2 plays an antinociceptive effect in nucleus accumbens of rats with neuropathic pain

The Journal of Physiological Sciences ◽

10.1186/s12576-021-00790-5 ◽

2021 ◽

Vol 71 (1) ◽

Author(s):

Yan Dong ◽

Chong-Yang Li ◽

Xiao-Min Zhang ◽

Ya-Nan Liu ◽

Shuang Yang ◽

...

Keyword(s):

Neuropathic Pain ◽

Nucleus Accumbens ◽

Pain Threshold ◽

Antinociceptive Effect ◽

Galanin Receptor ◽

Pain Model ◽

Withdrawal Threshold ◽

Neuropathic Pain Model ◽

Galanin Receptors ◽

Intact Rats

AbstractOur previous research has shown that galanin plays an antinociceptive effect via binding to galanin receptors (GalRs) in nucleus accumbens (NAc). This study focused on the involvement of GalR2 in galanin-induced antinociceptive effect in NAc of neuropathic pain rats. The chronic constriction injury of sciatic nerve (CCI) was used to mimic neuropathic pain model. The hind paw withdrawal latency (HWL) to thermal stimulation and hind paw withdrawal threshold (HWT) to mechanical stimulation were measured as the indicators of pain threshold. The results showed that 14 and 28 days after CCI, the expression of GalR2 was up-regulated in bilateral NAc of rats, and intra-NAc injection of GalR2 antagonist M871 reversed galanin-induced increases in HWL and HWT of CCI rats. Furthermore, intra-NAc injection of GalR2 agonist M1145 induced increases in HWL and HWT at day 14 and day 28 after CCI, which could also be reversed by M871. Finally, we found that M1145-induced antinociceptive effect in NAc of CCI rats was stronger than that in intact rats. These results imply that the GalR2 is activated in the NAc from day 14 to day 28 after CCI and GalR2 is involved in the galanin-induced antinociceptive effect in NAc of CCI rats.

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Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model

International Journal of Molecular Sciences ◽

10.3390/ijms22052479 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2479

Author(s):

Amir Mohammadzadeh ◽

Péter P. Lakatos ◽

Mihály Balogh ◽

Ferenc Zádor ◽

Dávid Árpád Karádi ◽

...

Keyword(s):

Neuropathic Pain ◽

Animal Studies ◽

Acute Administration ◽

Pain Model ◽

Therapeutic Value ◽

Small Doses ◽

Function Test ◽

Neuropathic Pain Model ◽

First Time ◽

Glycine Content

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.

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Buprenorphine: Far Beyond the “Ceiling”

Biomolecules ◽

10.3390/biom11060816 ◽

2021 ◽

Vol 11 (6) ◽

pp. 816

Author(s):

Rosmara Infantino ◽

Consalvo Mattia ◽

Pamela Locarini ◽

Antonio Luigi Pastore ◽

Sabatino Maione ◽

...

Keyword(s):

Quality Of Life ◽

Chronic Pain ◽

Neuropathic Pain ◽

Drug Abuse ◽

Side Effects ◽

National Health System ◽

Analgesic Drugs ◽

Third Line ◽

Dynamic Profile

Chronic pain, including neuropathic pain, represents an untreated disease with important repercussions on the quality of life and huge costs on the national health system. It is well known that opioids are the most powerful analgesic drugs, but they represent the second or third line in neuropathic pain, that remain difficult to manage. Moreover, these drugs show several side effects that limit their use. In addition, opioids possess addictive properties that are associated with misuse and drug abuse. Among available opioids compounds, buprenorphine has been suggested advantageous for a series of clinical reasons, including the effectiveness in neuropathic pain. Some properties are partly explained by its unique pharmacological characteristics. However, questions on the dynamic profile remain to be answered. Pharmacokinetics optimization strategies, and additional potentialities, are still to be explored. In this paper, we attempt to conceptualize the potential undiscovered dynamic profile of buprenorphine.

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