Abstract
BackgroundEnhanced supraspinal glutamate levels following nerve injury are associated with pathophysiological mechanisms responsible for neuropathic pain. Chronic pain can interfere with specific brain areas involved in glutamate-dependent neuropsychological processes, such as cognition, memory, and decision-making. The medial prefrontal cortex (mPFC) is thought to play a critical role in pain-related depression and anxiety, which are frequent co-morbidities of chronic pain. Using an animal model of spared nerve injury (SNI) of the sciatic nerve, we assess bio-molecular modifications in glutamatergic synapses in the mPFC that underlie neuropathic pain-induced plastic changes at 30 days post-surgery. Moreover, we examine the effects of palmitoylethanolamide (PEA) administration on pain-related behaviours, as well as the cortical biochemical and morphological changes that occur in SNI animals.ResultsAt 1 month, SNI was associated with mechanical and thermal hypersensitivity, as well as depression-like behaviour, cognitive impairments, and obsessive-compulsive activities. Moreover, we observed an overall glutamate synapse modification in the mPFC, characterized by changes in synaptic density proteins and amino acid levels. Finally, with regard to the resolution of pain and depressive-like syndrome in SNI mice, PEA restored the glutamatergic synapse proteins and changes in amino acid release.ConclusionsGiven the potential role of the mPFC in pain mechanisms, our findings may provide novel insights into neuropathic pain forebrain processes and indicate PEA as a new pharmacological tool to treat neuropathic pain and the related negative affective states.Graphical Palmitoylethanolamide: a new pharmacological tool to treat neuropathic pain and the related negative affective states.Electronic supplementary materialThe online version of this article (doi:10.1186/s13041-015-0139-5) contains supplementary material, which is available to authorized users.
Highlights
Enhanced supraspinal glutamate levels following nerve injury are associated with pathophysiological mechanisms responsible for neuropathic pain
NMDA-induced changes in dendritic plasticity has been shown in the prelimbic and infralimbic (PL-IL) cortex of neuropathic rats [15], whereas cortex deactivation has been shown in rodents with persistent inflammatory pain [16]
We found that repeated PEA treatment (10 mg/kg i.p., once per day) significantly increased both the thermal and mechanical thresholds in spared nerve injury (SNI) mice (7.8 s ± 0.5 and 7.4 g ± 0.4, respectively) 30 days after injury
Summary
Enhanced supraspinal glutamate levels following nerve injury are associated with pathophysiological mechanisms responsible for neuropathic pain. The medial prefrontal cortex (mPFC) is thought to play a critical role in pain-related depression and anxiety, which are frequent co-morbidities of chronic pain. Using an animal model of spared nerve injury (SNI) of the sciatic nerve, we assess bio-molecular modifications in glutamatergic synapses in the mPFC that underlie neuropathic pain-induced plastic changes at 30 days post-surgery. The medial prefrontal cortex (mPFC) is thought to play a key role in pain-related depression and anxiety, which are frequent co-morbidities of chronic pain [12, 13]. PL-IL cortex corresponds to the dorsal-lateral prefrontal cortex in primates It plays a crucial role in pain processing and pathological pain deeply affects its synaptic organization [7, 8, 14]. NMDA-induced changes in dendritic plasticity has been shown in the PL-IL cortex of neuropathic rats [15], whereas cortex deactivation has been shown in rodents with persistent inflammatory pain [16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
