Factors Besides Efficacy Guide Neuropathic Pain Treatment

The treatment of neuropathic pain remains a clinical challenge. Analgesic drugs and antidepressants are frequently ineffective, and opioids may induce side effects, including hyperalgesia. Recent results on brainstem pain modulatory circuits may explain those clinical challenges. The dual action of noradrenergic (NA) modulation was demonstrated in animal models of neuropathic pain. Besides the well-established antinociception due to spinal effects, the NA system may induce pronociception by directly acting on brainstem pain modulatory circuits, namely, at the locus coeruleus (LC) and medullary dorsal reticular nucleus (DRt). The serotoninergic system also has a dual action depending on the targeted spinal receptor, with an exacerbated activity of the excitatory 5-hydroxytryptamine 3 (5-HT3) receptors in neuropathic pain models. Opioids are involved in the modulation of descending modulatory circuits. During neuropathic pain, the opioidergic modulation of brainstem pain control areas is altered, with the release of enhanced local opioids along with reduced expression and desensitization of μ-opioid receptors (MOR). In the DRt, the installation of neuropathic pain increases the levels of enkephalins (ENKs) and induces desensitization of MOR, which may enhance descending facilitation (DF) from the DRt and impact the efficacy of exogenous opioids. On the whole, the data discussed in this review indicate the high plasticity of brainstem pain control circuits involving monoaminergic and opioidergic control. The data from studies of these neurochemical systems in neuropathic models indicate the importance of designing drugs that target multiple neurochemical systems, namely, maximizing the antinociceptive effects of antidepressants that inhibit the reuptake of serotonin and noradrenaline and preventing desensitization and tolerance of MOR at the brainstem.

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Neuropathic pain treatment: still a challenge

Neurology International ◽

10.4081/ni.2016.6322 ◽

2016 ◽

Vol 8 (2) ◽

Cited By ~ 6

Author(s):

Osvaldo J.M. Nascimento ◽

Bruno L. Pessoa ◽

Marco Orsini ◽

Pedro Ribeiro ◽

Eduardo Davidovich ◽

...

Keyword(s):

Neuropathic Pain ◽

Pain Control ◽

Pain Treatment ◽

Botulinum Toxin Type A ◽

Somatosensory System ◽

Botulinum Toxin Type ◽

Controlled Trials ◽

Channel Blockers ◽

Voltage Gated ◽

Randomized Controlled

Neuropathic pain (NP) is the result of a series of conditions caused by diseases or lesions to the somatosensory system. Due to the better understanding of NP pathophysiology previously unexplored therapies have been used with encouraging results. In this group, acetyl-L-carnitine, alpha-lipoic-acid, cannabinoids, clonidine, EMA401, botulinum toxin type A and new voltage-gated sodium channel blockers, can be included. Besides, changing paradigms may occur with the advent of optogenetics and a better understanding of epigenetic regulation. We reviewed the published literature on the pharmacological treatment of NP. Despite the interesting results, randomized controlled trials are demanded the majority of the therapies previously mentioned. In spite of several studies for the relief of NP, pain control continues being a challenge.

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Neuropathic pain treatment: a further step forward

The Lancet ◽

10.1016/s0140-6736(09)61205-8 ◽

2009 ◽

Vol 374 (9697) ◽

pp. 1218-1219 ◽

Cited By ~ 18

Author(s):

Troels Staehelin Jensen ◽

Nanna Brix Finnerup

Keyword(s):

Neuropathic Pain ◽

Pain Treatment

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Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain

BioMed Research International ◽

10.1155/2016/7917528 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 10

Author(s):

Eun Yeong Lim ◽

Yun Tai Kim

Keyword(s):

Neuropathic Pain ◽

Pain Relief ◽

Immune Responses ◽

Pain Treatment ◽

Physical Dependence ◽

Natural Compounds ◽

Number Of Patients ◽

Potential Benefits ◽

Somatosensory Nervous System ◽

Injury Causes

Neuropathic pain, defined as pain caused by a lesion or disease of the somatosensory nervous system, is characterized by dysesthesia, hyperalgesia, and allodynia. The number of patients with this type of pain has increased rapidly in recent years. Yet, available neuropathic pain medicines have undesired side effects, such as tolerance and physical dependence, and do not fully alleviate the pain. The mechanisms of neuropathic pain are still not fully understood. Injury causes inflammation and immune responses and changed expression and activity of receptors and ion channels in peripheral nerve terminals. Additionally, neuroinflammation is a known factor in the development and maintenance of neuropathic pain. During neuropathic pain development, the C-C motif chemokine receptor 2 (CCR2) acts as an important signaling mediator. Traditional plant treatments have been used throughout the world for treating diseases. We and others have identified food-derived compounds that alleviate neuropathic pain. Here, we review the natural compounds for neuropathic pain relief, their mechanisms of action, and the potential benefits of natural compounds with antagonistic effects on GPCRs, especially those containing CCR2, for neuropathic pain treatment.

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