Accepted

Neuropathic pain (NP) is a chronic pain condition resulting from a lesion or disease in the somatosensory nervous system. The aim of this study was to investigate the metabolome in plasma from patients with chronic peripheral, posttraumatic/postsurgical NP compared to healthy controls. Further, we aimed to investigate the correlation between pain intensity and the metabolome in plasma. The metabolic profile in plasma samples from 16 patients with chronic NP and 12 healthy controls was analyzed using a nuclear magnetic resonance spectroscopy method. Information about pain intensity, pain duration, body mass index (BMI), age, sex, and blood pressure were obtained through a questionnaire and clinical examination. Multivariate data analysis was used to identify metabolites significant for group separation and their correlation with pain intensity and duration, BMI, and age. We found 50 out of 326 features in plasma significantly contributing to group discrimination between NP and controls. Several of the metabolites that significantly differed were involved in inflammatory processes, while others were important for central nervous system functioning and neural signaling. There was no correlation between pain intensity and levels of metabolite in NP. These findings indicate that there seems to be peripheral/systemic differences in the metabolic profile between patients with chronic NP and healthy individuals.

Neuropathic pain is a common health problem resulting in exacerbated response to noxious and non noxious stimuli, as well as impaired emotional and cognitive responses. Unfortunately, neuropathic pain is also one of the most difficult pain syndromes to manage, highlighting the importance of better understanding the brain regions and neuromodulatory mechanisms involved in its regulation. Among the many interconnected brain areas which process pain, the amygdala is known to play an important role in the integration of sensory and emotional pain signals. Here we questioned the ability of a recently identified neuromodulatory mechanism associated with the metabotropic glutamate receptors mGlu in the amygdala to modulate neuropathic pain. In a murine model of peripheral mononeuropathy, we demonstrate that pharmacological activation of amygdala mGlu efficiently alleviates sensory and depressive-like symptoms in both male and female mice. Moreover, we reveal a differential modulation of these symptoms. Activating mGlu in the contralateral amygdala relative to the side of the mononeuropathy, is necessary and sufficient to relieve both sensory and depressive-like symptoms, while ipsilateral activation solely reduces depressive-like symptoms. Furthermore, using photopharmacology, a recent strategy allowing precise photocontrol of endogenous proteins, we further demonstrate the dynamic alleviation of neuropathic pain through light-dependent facilitation of mGlu by a photoswitchable positive allosteric modulator. Finally, coupling photopharmacology and analgesic conditioned place preference, we show a significant pain-reducing effect of mGlu4 activation. Taken together, these data highlight the analgesic potential of enhancing amygdala mGlu activity to counteract neuropathy reinforcing its therapeutic interest for the treatment of pathological pain.

Peripheral nerve stimulation (PNS) is an effective neuromodulation therapy for chronic neuropathic and nociceptive pain. Although the total number of PNS implantations has increased over the last decade, no curriculum exists to guide training and learning of this therapy. The goal of the North American Neuromodulation Society (NANS) education committee is to develop a series of competency-based curriculums for neuromodulation therapies. The PNS curriculum is the latest part of such series, following the curriculums for spinal cord stimulation and intrathecal drug delivery system.

Spinal cord stimulator (SCS) placement has been gaining traction as an approach to modulate pain levels for several different chronic pain conditions. This procedure can be performed via a percutaneous or open approach. Data regarding SCS complications are relatively limited.

Central sensitization (CS) is defined as increased responsiveness of nociceptive neurons in the central nervous system to normal or subthreshold afferent input. The CS phenomenon is caused by continuous, intense nociceptor inputs triggering a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in the central nociceptive pathway. Most patients undergoing surgery for lumbar spinal stenosis (LSS) experience symptoms for more than three months; therefore, it is possible that CS is associated with postoperative symptoms of LSS. The aim of this study was to clarify the influence of CS in patients who underwent surgery for LSS.

Migraine involves central and peripheral nervous system mechanisms. Erenumab, an anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody with little central nervous system penetrance, is effective for migraine prevention. The objective of this study was to determine if response to erenumab is associated with alterations in brain functional connectivity and pain-induced brain activations.