scholarly journals Opioids and Neuropathic Pain

2012 ◽  
Vol 3S;15 (3S;7) ◽  
pp. ES93-ES110
Author(s):  
Howard S. Smith
Keyword(s):  
Neuropathic Pain ◽  
Opioid Therapy ◽  
Chronic Neuropathic Pain ◽  
Analgesic Tolerance ◽  
Key Words Pain ◽  
Analgesic Agents ◽  
Opioid Induced Hyperalgesia ◽  
Third Line ◽  
Effective Analgesia ◽  
Better Than

Opioids are broad spectrum analgesics that may be beneficial to alleviate the intense perception of algesia in patients suffering with pain. They have been one of the most controversial analgesics, in part because of their potential for addiction. Opioids or any currently available analgesic will not provide effective analgesia for every patient with chronic neuropathic pain (NP), but overall opioids are considered to be a second or third line class of analgesics that may provide reasonable analgesia to some patients with chronic NP. Although opioids may alleviate chronic NP, overall, NP tends to be less opioid responsive than nociceptive pain. The mechanisms that may contribute to neuropathic pain may simultaneously also contribute to diminishing the antinociceptive properties of opioids for neuropathic pain. Some of these mechanisms may also contribute to analgesic tolerance and/or opioid-induced hyperalgesia. Hyperalgesia consequently to nerve insult and opioidinduced analgesic tolerance, may both involve the N-methyl-D-aspartate (NMDA) receptor and share part of intracellular events producing a state of neural hyperexcitation. Conversely, opioid therapy may contribute to nociceptive processes that may be involved in neuropathic pain such as opioid-induced cholecystokinin release. Furthermore, within NP, peripheral NP appears to be the most opioid responsive, followed by spinal NP while supraspinal NP tends to be the least responsive to opioids. Although, there is no robust evidence that any specific opioid agent is better than any other opioid at effectively treating NP, it is conceivable that some opioids/opioid-like analgesic agents may be particularly well suited to alleviate NP in certain patients suffering from neuropathic pain. Key words: Pain, neuropathic, opioids, oxycodone, methadone, buprenorphine, tramadol, tapentadol

scholarly journals Carbamazepine Withdrawal-induced Hyperalgesia in Chronic Neuropathic Pain

2015 ◽  
Vol 6;18 (6;11) ◽  
pp. E1127-E1130
Author(s):  
Suodi Zhai
Keyword(s):  
Neuropathic Pain ◽  
Rodent Models ◽  
Pharmacological Treatments ◽  
Chronic Neuropathic Pain ◽  
Antiepileptic Agent ◽  
Opioid Induced Hyperalgesia ◽  
Key Words Analgesia ◽  
Third Line ◽  
Pain Patients ◽  
Potential Use

Combined pharmacological treatments are the most used approach for neuropathic pain. Carbamazepine, an antiepileptic agent, is generally used as a third-line treatment for neuropathic pain and can be considered an option only when patients have not responded to the first- and second-line medications. In the case presented herein, a patient with neuropathic pain was treated using a combined pharmacological regimen. The patient’s pain deteriorated, despite increasing the doses of opioids, when carbamazepine was discontinued, potentially because carbamazepine withdrawal disrupted the balance that was achieved by the multifaceted pharmacological regimen, thus inducing hyperalgesia. Interestingly, when carbamazepine was prescribed again, the patient’s pain was successfully managed. Animal research has reported that carbamazepine can potentiate the analgesic effectiveness of morphine in rodent models of neuropathic pain and postoperative pain. This clinical case demonstrates that carbamazepine may have a synergistic effect on the analgesic effectiveness of morphine and may inhibit or postpone opioid-induced hyperalgesia. We postulate that a probable mechanism of action of carbamazepine may involve -aminobutyric acid-ergic potentiation and the interruption of glutamatergic function via N-methyl-D-aspartate receptors. Further research is warranted to clarify the analgesic action of carbamazepine and its potential use for the prevention of opioidinduced hyperalgesia in chronic neuropathic pain patients. Key words: Analgesia, hyperalgesia, carbamazepine, opioids, neuropathic pain, pharmacologic treatment

scholarly journals Pharmacological Management of Chronic Neuropathic Pain – Consensus Statement and Guidelines from the Canadian Pain Society

2007 ◽  
Vol 12 (1) ◽  
pp. 13-21 ◽  
Author(s):  
DE Moulin ◽  
AJ Clark ◽  
I Gilron ◽  
MA Ware ◽  
CPN Watson ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Controlled Trial ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Ease Of Use ◽  
Control Group ◽  
Pharmacological Management ◽  
Randomized Controlled ◽  
Analgesic Agents ◽  
Third Line

Neuropathic pain (NeP), generated by disorders of the peripheral and central nervous system, can be particularly severe and disabling. Prevalence estimates indicate that 2% to 3% of the population in the developed world suffer from NeP, which suggests that up to one million Canadians have this disabling condition. Evidence-based guidelines for the pharmacological management of NeP are therefore urgently needed. Randomized, controlled trials, systematic reviews and existing guidelines focusing on the pharmacological management of NeP were evaluated at a consensus meeting. Medications are recommended in the guidelines if their analgesic efficacy was supported by at least one methodologically sound, randomized, controlled trial showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment are based on degree of evidence of analgesic efficacy, safety, ease of use and cost-effectiveness. Analgesic agents recommended for first-line treatments are certain antidepressants (tricyclics) and anticonvulsants (gabapentin and pregabalin). Second-line treatments recommended are serotonin noradrenaline reuptake inhibitors and topical lidocaine. Tramadol and controlled-release opioid analgesics are recommended as third-line treatments for moderate to severe pain. Recommended fourth-line treatments include cannabinoids, methadone and anticonvulsants with lesser evidence of efficacy, such as lamotrigine, topiramate and valproic acid. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes, and treatment of pediatric and central NeP.

scholarly journals Use of Methadone for Neuropathic Pain

2003 ◽  
Vol 8 (3) ◽  
pp. 131-132 ◽  
Author(s):  
Dwight Moulin
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Nerve Injury ◽  
Opioid Analgesics ◽  
Common Complication ◽  
Chronic Neuropathic Pain ◽  
High Quality ◽  
Antidepressant Treatments ◽  
High Quality Evidence ◽  
Effective Analgesia ◽  
Quality Evidence

Chronic neuropathic pain is often considered to be a common complication of injury to the central or peripheral nervous system and the pain itself is usually assumed to be intractable. Both of these assumptions are inaccurate. For example, numbness and tingling in glove and stocking distribution are common accompaniments of longstanding diabetes mellitus, but only about 10% of patients with diabetic neuropathy consider these sensory changes to be painful (1). Anticonvulsant and antidepressant treatments provide effective analgesia in up to 50% of patients with chronic neuropathic pain (2) and there is a growing body of high-quality evidence that controlled-release opioid analgesics provide substantial pain relief in a further subset of patients (3-6). Even with polypharmacy, this still leaves perhaps 20% to 30% of chronic neuropathic pain sufferers lacking adequate analgesia, and side effects can be problematic. In addition, central pain appears to be more refractory to opioid treatment than pain due to peripheral nerve injury (7).

scholarly journals Combination Opioid Analgesics

2008 ◽  
Vol 2;11 (3;2) ◽  
pp. 201-214
Author(s):  
Howard Smith
Keyword(s):  
Adverse Effects ◽  
Opioid Analgesic ◽  
Analgesic Efficacy ◽  
Opioid Analgesics ◽  
Active Metabolites ◽  
Analgesic Tolerance ◽  
Key Words Pain ◽  
Long Duration ◽  
Wide Range ◽  
Opioid Induced Hyperalgesia

Although there is no “ideal analgesic,” scientists and clinicians alike continue to search for compounds with qualities which may approach the “ideal analgesic.” Characteristics of an “ideal” analgesic may include: the agent is a full agonist providing optimal/maximal analgesia for a wide range/variety of pain states (e.g., broad spectrum analgesic activity), it does not exhibit tolerance, it produces no unwanted effects and minimal adverse effects, it has no addictive potential, it does not facilitate pain/hyperalgesia, it has a long duration, it has high oral bioavailability, it is not vulnerable to important drug interactions, it is not significantly bound to plasma proteins, it has no active metabolites, it has linear kinetics, and it is eliminated partly by hydrolysis to an inactive metabolite (without involvement of oxidative and conjugative enzymes). Investigators have concentrated on ways to alter existing analgesics or to combine existing analgesic compounds with compounds which may improve efficacy over time or minimize adverse effects. The addition of an analgesic with a second agent (which may or may not also be an analgesic) to achieve a “combination analgesic” is a concept which has been exploited for many years. Although there may be many reasons to add 2 agents together in efforts to achieve analgesia, for purposes of this article — reasons for combining an opioid with a second agent to produce a combination opioid analgesic may be classified into 6 major categories: 1.) combinations to prolong analgesic duration; 2.) combinations to enhance or optimize analgesic efficacy (e.g., analgesic synergy); 3.) combinations to diminish or minimize adverse effects; 4.) combinations to diminish opioid effects which are not beneficial (or contrariwise to or enhance beneficial opioid effects); 5.) combinations to reduce opioid tolerance/opioid-induced hyperalgesia; and 6.) combinations to combat dependency issues/addiction potential/craving sensations. Combination opioid analgesics are one avenue which may give rise to “pain pills” with improved analgesic profiles over existing analgesic medications. Key words: Pain, combination opioid analgesic, tolerance, opioid-induced hyperalgesia

scholarly journals Sex Differences in Tolerance to Delta-9-Tetrahydrocannabinol in Mice With Cisplatin-Evoked Chronic Neuropathic Pain

2021 ◽  
Vol 8 ◽  
Author(s):  
Angela N. Henderson-Redmond ◽  
LaTaijah C. Crawford ◽  
Diana E. Sepulveda ◽  
David E. Hale ◽  
Julia J. Lesperance ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sex Differences ◽  
Neuropathic Pain ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Preclinical Research ◽  
Chronic Neuropathic Pain ◽  
Analgesic Tolerance ◽  
Increased Sensitivity ◽  
Males And Females

Tolerance to the pain-relieving effects of cannabinoids limits the therapeutic potential of these drugs in patients with chronic pain. Recent preclinical research with rodents and clinical studies in humans has suggested important differences between males and females in the development of tolerance to cannabinoids. Our previous work found that male mice expressing a desensitization resistant form (S426A/S430A) of the type 1 cannabinoid receptor (CB1R) show delayed tolerance and increased sensitivity to the antinociceptive effects of delta-9-tetrahydrocannabinol (∆9-THC). Sex differences in tolerance have been reported in rodent models with females acquiring tolerance to ∆9-THC faster than males. However, it remains unknown whether the S426A/S430A mutation alters analgesic tolerance to ∆9-THC in mice with chemotherapy-evoked chronic neuropathic pain, and also whether this tolerance might be different between males and females. Male and female S426A/S430A mutant and wild-type littermates were made neuropathic using four once-weekly injections of 5 mg/kg cisplatin and subsequently assessed for tolerance to the anti-allodynic effects of 6 and/or 10 mg/kg ∆9-THC. Females acquired tolerance to the anti-allodynic effects of both 6 and 10 mg/kg ∆9-THC faster than males. In contrast, the S426A/S430A mutation did not alter tolerance to ∆9-THC in either male or female mice. The anti-allodynic effects of ∆9-THC were blocked following pretreatment with the CB1R antagonist, rimonabant, and partially blocked following pretreatment with the CB2R inverse agonist, SR144528. Our results show that disruption of the GRK/β-arrestin-2 pathway of desensitization did not affect sensitivity and/or tolerance to ∆9-THC in a chronic pain model of neuropathy.

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