scholarly journals Multifunctional Opioid-Derived Hybrids in Neuropathic Pain: Preclinical Evidence, Ideas and Challenges

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5520
Author(s):  
Joanna Starnowska-Sokół ◽  
Barbara Przewłocka
Keyword(s):  
Neuropathic Pain ◽  
Rational Design ◽  
Tissue Injury ◽  
Biological Action ◽  
Nerve Tissue ◽  
Compensatory Mechanisms ◽  
Painful Neuropathy ◽  
Analgesic Effects ◽  
Opioid Agonists ◽  
Hybrid Drugs

When the first- and second-line therapeutics used to treat neuropathic pain (NP) fail to induce efficient analgesia—which is estimated to relate to more than half of the patients—opioid drugs are prescribed. Still, the pathological changes following the nerve tissue injury, i.a. pronociceptive neuropeptide systems activation, oppose the analgesic effects of opiates, enforcing the use of relatively high therapeutic doses in order to obtain satisfying pain relief. In parallel, the repeated use of opioid agonists is associated with burdensome adverse effects due to compensatory mechanisms that arise thereafter. Rational design of hybrid drugs, in which opioid ligands are combined with other pharmacophores that block the antiopioid action of pronociceptive systems, delivers the opportunity to ameliorate the NP-oriented opioid treatment via addressing neuropathological mechanisms shared both by NP and repeated exposition to opioids. Therewith, the new dually acting drugs, tailored for the specificity of NP, can gain in efficacy under nerve injury conditions and have an improved safety profile as compared to selective opioid agonists. The current review presents the latest ideas on opioid-comprising hybrid drugs designed to treat painful neuropathy, with focus on their biological action, as well as limitations and challenges related to this therapeutic approach.

Benzimidazole Derivative Ameliorates Opioid-mediated Tolerance during Anticancer-Induced Neuropathic Pain in mice

2020 ◽  
Vol 20 ◽  
Author(s):  
Sana Akhtar ◽  
Muzaffar Abbas ◽  
Komal Naeem ◽  
Muhammad Faheem ◽  
Humaira Nadeem ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Cancer Patients ◽  
Benzimidazole Derivative ◽  
Chemotherapeutic Agents ◽  
Drug Candidate ◽  
Tail Flick ◽  
Painful Neuropathy ◽  
Analgesic Effects ◽  
Tnf Α ◽  
Induced Tolerance

Background: Cancer is known to be the second significant cause of death worldwide. Chemotherapeutic agents such as platinum-based compounds are frequently used single-handedly or accompanied with additional chemotherapies to treat cancer patients. Chemotherapy-inducedperipheral painful neuropathy is seen in around 40% of patient who are treated with platinum-based compounds including cisplatin. This not only decreases quality of life of patients but also patients’ compliance to cisplatin. Objectives: Nalbuphine, an opioid, is frequently used to treat acute and chronic pain coupled with cisplatin in cancer patients. However, long term use of nalbuphine induces tolerance to its analgesic effects. We employed the same strategy to induce tolerance in mice. Methods: Here, we investigated analgesic effects of 2-[(pyrrolidin-1-yl) methyl]-1H-benzimidazole (BNZ), a benzimidazole derivative, on nalbuphine-induced tolerance during cisplatin-induced neuropathic pain using hot plate test, tail flick tests andvon Frey filament in mouse models. Furthermore, we investigated the effects of BNZ on the expression of tumor necrosis factor alpha (TNF-α) in spinal cord. Results: The results showed that BNZ reduced tolerance to analgesic effects of nalbuphine and TNF-α expression in mice. Conclusion: BNZ could be potential drug candidate for the management of nalbuphine-induced tolerance in cisplatin-induced neuropathicpain.

scholarly journals Analgesic effects of ketamine infusion therapy in korean patients with neuropathic pain: A 2-week, open-label, uncontrolled study

2010 ◽  
Vol 71 (2) ◽  
pp. 93-104 ◽  
Author(s):  
Jin Gu Kang ◽  
Chul Joong Lee ◽  
Tae Hyeong Kim ◽  
Woo Seok Sim ◽  
Byung Seop Shin ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Infusion Therapy ◽  
Open Label ◽  
Ketamine Infusion ◽  
Uncontrolled Study ◽  
Korean Patients ◽  
Analgesic Effects

scholarly journals Analgesic effects of a hydro-ethanolic whole plant extract of Synedrella nodiflora (L.) Gaertn in paclitaxel-induced neuropathic pain in rats

2017 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick Amoateng ◽  
Samuel Adjei ◽  
Dorcas Osei-Safo ◽  
Kennedy Kwami Edem Kukuia ◽  
Irene Akwo Kretchy ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Plant Extract ◽  
Analgesic Effects ◽  
Whole Plant ◽  
Synedrella Nodiflora

scholarly journals The effect of baclofen on spontaneous and evoked behavioural expression of experimental neuropathic chronic pain

1999 ◽  
Vol 57 (3B) ◽  
pp. 753-760 ◽  
Author(s):  
TEREZINHA DE JESUS T. SANTOS ◽  
CARLOS M. DE CASTRO-COSTA ◽  
SÍLVIO D. A. GIFFONI ◽  
FRANKLIN J. C. SANTOS ◽  
RODRIGO S. N. RAMOS ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Aminobutyric Acid ◽  
Thermal Stimulus ◽  
Dependent Manner ◽  
Gamma Aminobutyric Acid ◽  
Analgesic Effects ◽  
Nociceptive Stimulus ◽  
Dose Dependent

Baclofen (beta-p-chlorophenyl-GABA) has been used in humans to treat spasticity, as well as trigeminal neuralgia. Since GABA (gamma-aminobutyric acid) has been implicated in inhibitory and analgesic effects in the nervous system, it was of interest to study the effect of baclofen in experimental neuropathic pain. With this purpose, experiments were carried out in 17 neuropathic rats with constrictive sciatic injury, as described by Bennet and Xie (1988), taking as pain parameters scratching behaviour and the latency to the thermal nociceptive stimulus. The results showed that baclofen induces, in a dose-dependent manner, significant decrease (p < 0.05) of scratching behaviour and significant increase (p < 0.05) of the latency to the nociceptive thermal stimulus. The absence of antagonism of naloxone suggested a non-participation of an opioid-mediated mechanism in this analgesic effect of baclofen on experimental neuropathic pain.

scholarly journals The refined biomimetic NeuroDigm GEL™ Model of neuropathic pain in the mature rat

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2516 ◽  
Author(s):  
Mary R. Hannaman ◽  
Douglas A. Fitts ◽  
Rose M. Doss ◽  
David E. Weinstein ◽  
Joseph L. Bryant
Keyword(s):  
Neuropathic Pain ◽  
Recombinant Human Erythropoietin ◽  
Tissue Injury ◽  
Soft Tissue Injury ◽  
Pain Behavior ◽  
Neural Regeneration ◽  
Male Rat ◽  
Human Erythropoietin ◽  
Neural Remodeling ◽  
Over Time

Background:Many humans suffering with chronic pain have no clinical evidence of a lesion or disease. They are managed with a morass of drugs and invasive procedures. Opiates usually become less effective over time. In many, their persistent pain occurs after the healing of a soft tissue injury. Current animal models of neuropathic pain typically create direct neural damage with open surgeries using ligatures, neurectomies, chemicals or other forms of deliberate trauma. However, we have observed clinically that after an injury in humans, the naturally occurring process of tissue repair can cause chronic neural pain.Methods:We demonstrate how the refined biomimetic NeuroDigm GEL™ Model, in the mature male rat, gradually induces neuropathic pain behavior with a nonsurgical percutaneous implant of tissue-derived hydrogel in the musculo-fascial tunnel of the distal tibial nerve. Morphine, Celecoxib, Gabapentin and Duloxetine were each screened in the model three times each over 5 months after pain behaviors developed. A pilot study followed in which recombinant human erythropoietin was applied to the GEL neural procedure site.Results:The GEL Model gradually developed neuropathic pain behavior lasting months. Morphine, initially effective, had less analgesia over time. Celecoxib produced no analgesia, while gabapentin and duloxetine at low doses had profound analgesia at all times tested. The injected erythropoietin markedly decreased bilateral pain behavior that had been present for over 4 months. Histology revealed a site of focal neural remodeling, with neural regeneration, as in human biopsies.Conclusion:The refined NeuroDigm GEL™ Model induces localized neural remodeling resulting in robust neuropathic pain behavior. The analgesics responses in this model reflect known responses of humans with neuropathic pain. The targeted recombinant human erythropoietin appears to heal the ectopic focal neural site, as demonstrated by the extinguishing of neuropathic pain behavior present for over 4 months.

Combination of inhaled nitrous oxide and oral opioids induces long lasting analgesic effects in patients with neuropathic pain

Pain ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Didier Bouhassira ◽  
Serge Perrot ◽  
Nadine Attal ◽  
Juan Fernando Ramirez-Gil ◽  
Cécile Delval ◽  
...  
Keyword(s):  
Nitrous Oxide ◽  
Neuropathic Pain ◽  
Analgesic Effects

Drugs for neuropathic pain

2021 ◽  
pp. 500-510
Author(s):  
Sachin Rastogi ◽  
Fiona Campbell
Keyword(s):  
Neuropathic Pain ◽  
Drug Therapy ◽  
Side Effects ◽  
Randomized Controlled Trials ◽  
Tissue Injury ◽  
Somatosensory System ◽  
Pain Syndrome ◽  
Direct Consequence ◽  
Controlled Trials ◽  
Pharmacological Management

Neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system.” It is often contrasted with nociceptive pain, which is associated with tissue injury or inflammation. Neuropathic pain conditions in children are qualitatively different from those common in adults and include complex regional pain syndrome, postoperative neuropathic pain, and autoimmune and degenerative neuropathies. Few randomized controlled trials in pediatrics means that evidence from adult studies is extrapolated to guide pharmacological management in children, which is problematic as the etiologies and mechanisms are different. An algorithm for drug therapy is proposed based on the best-available evidence, clinical experience, and the safety of these drugs in pediatric practice. A step-wise approach should be tried methodically according to effectiveness and side effects. Neuropathic pain in children, if identified and treated in a timely manner as part of an interprofessional framework, can be managed effectively.

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