Combination pharmacotherapy for neuropathic pain: current evidence and future directions

Abstract

Current drugs reduce neuropathic pain and improve mood and quality of life. However, as single agents they are limited by incomplete efficacy and dose-limiting adverse effects. Recent experimental and clinical data support the potential of combination pharmacotherapy for neuropathic pain. Therapeutic benefits may include greater efficacy, lower doses and fewer adverse effects. Due to potential adverse, as well as beneficial, drug interactions, safety and efficacy of specific combinations must be empirically evaluated. Techniques such as isobolographic analysis, response-surface modeling and other model-free tests have been used in order to characterize analgesic interactions as antagonistic, additive or synergistic. Whether synergistic or not, a clinically useful combination could simply have additive or even subadditive analgesia, provided that there is less additivity for side effects. Despite widespread clinical use, there are surprisingly few published observations on combination therapy for neuropathic pain. This review discusses future directions and proposes research strategies aimed at bridging current knowledge gaps, including safety, compliance and cost-effectiveness; discovering optimal drug combinations and dose ratios; comparing concurrent with sequential combination therapy; and combining more than two drugs. Continued close integration of basic and clinical sciences is crucial in further harnessing the potential of combination pharmacotherapy in neuropathic pain.

Recent and Emerging Trends in Pharmacotherapy of Neuropathic Pain

“…CB1 receptors are mainly present in CNS andCB2 are located in the periphery, particularly in immune cells. [59] CB1 receptor-dependent retrograde mechanism in the CNS has been found to cause the release of neurotransmitters controlling pain inputs and inflammation. Recent studies suggest the role oromucosal extracts of cannabis analogs (nabilone, dronabinol and tetrahydrocannabinol) analogue in NP.…”

“…Peripherally acting (at dorsal root ganglia and spinal cord) CB2 agonists are under development for the treatment of NP disorders as CB1 receptor activation produces many CNS adverse effects. [59,61,62] Oromucosal cannabinoids (2.7 mg delta-9-tetrahydrocannabinol/ 2.5 mg cannabidiol) have been found effective in pain associated with multiple sclerosis and in refractory peripheral NP associated with allodynia. It has been found that around 90% of the patients experienced adverse effects and one-third of the patients withdrew due to lack of efficacy or due to adverse drug reactions.…”

Efficacy of selected complementary and alternative medicine interventions for chronic pain

“…More recently, substantial evidence indicates that acupuncture is also effective in treating chronic LBP [134][135] and support for the efficacy of acupuncture for premenstrual syndrome has been published in China [136]. One reviewer found that results from studies on efficacy are considered (1) positive by some and difficult to interpret by others for the treatment of migraine and TMJ disorders; (2) promising for fibromyalgia, knee OA, and tennis elbow, although additional research is needed; and (3) inconclusive or difficult to interpret for neck pain [137].…”

“…In this way, any potential benefits of the individual treatments can combine for maximum pain relief for the patient. Interest in combined traditional medical treatments for maximum pain relief is increasing, but no reason exists that more established CAM modalities should not at least be considered during development of multimodal treatment plans [137]. Additional research must examine the use of individual CAM therapies with other CAM approaches and with traditional interventions in terms of safety and synergistic effects.…”

Analysis of the Efficacy of the Lidocaine Patch 5% in the Treatment of Neuropathic Pain: Our Feedback

“…Treatment with only one drug is usually ineffective and, in the majority of cases, a combination is given, depending on the severity and qualities of the pain and on any comorbidity [6].…”