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Neuropathic pain (NP) is present in 40-to-50% of spinal cord injured patients. It tends to chronicity and correlates with lower quality-of-life. Moreover, the role of NP in the eventual exacerbation of anxiety- and depression-like behaviours during its development and chronification in genetically susceptible individuals remains unclear. Thus, although solely few animal models are available, new specific models are needed to complete the array of chances to assay new therapeutic strategies with the aim of treating chronic NT and its associated mood disorders. The present study was conceived to evaluate hyperalgesic responses and anxiety- and depression-like behaviours after graded photochemical spinal cord injury (SCI) up to chronic phase. BALB/c strain was used: it expresses a phenotype characterized by high innate anxiety levels, allowing to elucidate whether NP may exacerbate mood disorders at SCI chronic phase. After different photoinduction-times on exposed spinal cord, the mice developed a graded chronic hyperalgesia with minor to non-existent motor dysfunction. Behavioural data suggest that whilst hyperalgesia associated to SCI does not exacerbate BALB/c anxiety-like behaviours, it may result in depression-like behaviour at SCI chronic phase. Our study demonstrates that chronic central hyperalgesia may exacerbate despair-like behaviour at the SCI chronic phase in a mouse model of high anxiety-related behaviour. This implies that photochemical-SCI may be a suitable model to study the comorbidity between chronic NP and mood disorders.

(-)-Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the neuropathic pain alleviation in animal models. Because chemokine fractalkine (CX3CL1) has been suggested as an important signal during neuropathic pain development, this study aimed to investigate whether CX3CL1 expression may be modulated by EGCG treatment reducing hyperalgesia in chronic constriction injured mice. To this end, Balb/c mice were subjected to a chronic constriction injury of sciatic nerve (CCI) and treated with EGCG or vehicle once a day during the first week following surgery. Thermal hyperalgesia was tested at 7 and 14 days post-surgery, and the expression of CX3CL1 and its mRNA were analyzed in spinal cord at the end of the experimental period. Results revealed that EGCG treatment significantly reduced thermal hyperalgesia in CCI-injured mice at short time, and this antihyperalgesic effect was associated with a down-regulation of CX3CL1 protein expression in the spinal cord. On the other hand, EGCG treatment did not affect the CX3CL1 transcription. Overall, our results suggest a new role of EGCG-treatment in an experimental model of neuropathic pain as a mediator of nociceptive signaling cross talk between neurons and glial cells in the dorsal horn of the spinal cord. Copyright © 2016 John Wiley & Sons, Ltd.

Background (−)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic constituent found in green tea. It has been reported that may be a natural agent for reducing thermal and mechanical pain after nervous system injuries. However, the molecular pathways implicated in these beneficial effects have not been completely elucidated. This study aimed to assess the EGCG treatment effects on thermal hyperalgesia, spinal cord gliosis and modulation of Ras homologue gene family member A (RhoA), fatty acid synthase (FASN) and tumour necrosis factor alpha (TNF-α) expression after spinal cord contusion in mice. Methods Animals were subjected to a spinal cord contusion. Thirty minutes after contusion and daily during the first week post-surgery, animals were treated with EGCG or dimethyl sulfoxide-saline (DMSO-saline). At 7 and 14 days post-operation, motor recovery was evaluated using the Basso Mouse Scale, and nociceptive response was evaluated using the Hargreaves test. Furthermore, at 14 days, the expression of RhoA, FASN and TNF-α proteins was quantified in the lesion site of spinal cord by Western blot technique. Finally, spinal cord samples were processed by immunohistochemical techniques for observing astrocytes, microglia and afferent nerve fibres. Results At short time, EGCG treatment reduced significantly thermal hyperalgesia but had no effect on locomotor recovery in spinal cord injured mice. Furthermore, EGCG treatment down-regulated the RhoA, FASN and TNF-α proteins expression, and decreased astro- and microglia reactivity in spinal cord. Conclusion These findings suggest that at short time EGCG treatment reduces thermal hyperalgesia and gliosis via FASN and RhoA pathway, causing a decrease in cytokines in spinal cord.

This is a narrative review of the literature. This review aims to be useful in identifying therapeutic targets. It focuses on the molecular and biochemical neuroplasticity changes that occur in the somatosensory system, including ascending and descending pathways, during the development of neuropathic pain. Furthermore, it highlights the latest experimental strategies, based on the changes reported in the damaged nociceptive neurons during neuropathic pain states. This study was conducted in Girona, Catalonia, Spain. A MEDLINE search was performed using the following terms: descending pain pathways; ascending pain pathways; central sensitization; molecular pain; and neuropathic pain pharmacological treatment. Neuropathic pain triggered by traumatic lesions leads to sensitization and hyperexcitability of nociceptors and projection neurons of the dorsal horn, a strengthening in the descendent excitatory pathway and an inhibition of the descending inhibitory pathway of pain. These functional events are associated with molecular plastic changes such as overexpression of voltage-gated ion channels, algogen-sensitive receptors and synthesis of several neurotransmitters. Molecular studies on the plastic changes in the nociceptive somatosensory system enable the development of new pharmacological treatments against neuropathic pain, with higher specificity and effectiveness than classical drug treatments. Although research efforts have already focused on these aspects, additional research may be necessary to further explore the potential therapeutic targets in neuropathic pain involved in the neuroplasticity changes of neuropathological pathways from the injured somatosensory system.