Articles: neuralgia.
-
Anesthesia and analgesia · Dec 2023
Phosphate NIMA-Related Kinase 2-Dependent Epigenetic Pathways in Dorsal Root Ganglion Neurons Mediates Paclitaxel-Induced Neuropathic Pain.
The microtubule-stabilizing drug paclitaxel (PTX) is an important chemotherapeutic agent for cancer treatment and causes peripheral neuropathy as a common side effect that substantially impacts the functional status and quality of life of patients. The mechanistic role for NIMA-related kinase 2 (NEK2) in the progression of PTX-induced neuropathic pain has not been established. ⋯ pRSK2/JMJD3/H3K27me3/TRPV1 signaling in the DRG neurons plays as a key regulator for PTX therapeutic approaches.
-
Journal of neurotrauma · Dec 2023
Relating spinal injury-induced neuropathic pain and spontaneous afferent activity to sleep and respiratory dysfunction.
Abstract Spinal cord injury (SCI) can induce dysfunction in a multitude of neural circuits including those that lead to impaired sleep, respiratory dysfunction, and neuropathic pain. We used a lower thoracic rodent contusion SCI model of neuropathic pain that has been shown to associate with increased spontaneous activity in primary afferents and hindlimb mechanosensory stimulus hypersensitivity. Here we paired capture of these variables with chronic capture of three state sleep and respiration to more broadly understand SCI-induced physiological dysfunction and to assess possible interrelations. ⋯ Hindlimb mechanosensitivity was assessed weekly, and terminal experiments measured primary afferent spontaneous activity in situ from intact lumbar dorsal root ganglia (DRG). We observed that SCI led to increased spontaneous primary afferent activity (both firing rate and the number of spontaneously active DRGs) that correlated with increased respiratory rate variability and measures of sleep fragmentation. This is the first study to measure and link sleep dysfunction and variability in respiratory rate in a SCI model of neuropathic pain, and thereby provide broader insight into the magnitude of overall stress burden initiated by neural circuit dysfunction after SCI.
-
Neuromodulation has been successfully used globally to address severe refractory chronic pain for over five decades. Compared to the wide acceptance that it enjoys in United States and Europe, it is fairly underutilized in Asia, including India. ⋯ The younger generation of pain practitioners in India is becoming more aware and convinced about the role of neuromodulation to alleviate severe pain and suffering. An all-round approach combining improved training, awareness at various levels, more flexible options of newer technology and reimbursement approval can positively influence its use. This can be achieved with the collective efforts of physicians, insurers, industry, and focused academic activities of clinical societies.
-
Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that binds numerous ligands including vascular endothelial growth factor A (VEGFA). Binding of this ligand to NRP-1 and the co-receptor, the tyrosine kinase receptor VEGFR2, elicits nociceptor sensitization resulting in pain through the enhancement of the activity of voltage-gated sodium and calcium channels. We previously reported that blocking the interaction between VEGFA and NRP-1 with the Spike protein of SARS-CoV-2 attenuates VEGFA-induced dorsal root ganglion (DRG) neuronal excitability and alleviates neuropathic pain, pointing to the VEGFA/NRP-1 signaling as a novel therapeutic target of pain. ⋯ Following in vivo editing of NRP-1, lumbar dorsal horn slices showed a decrease in the frequency of VEGFA-mediated increases in spontaneous excitatory postsynaptic currents. Finally, intrathecal injection of a lentivirus packaged with an NRP-1 guide RNA and Cas9 enzyme prevented spinal nerve injury-induced mechanical allodynia and thermal hyperalgesia in both male and female rats. Collectively, our findings highlight a key role of NRP-1 in modulating pain pathways in the sensory nervous system.
-
Postherpetic neuralgia (PHN) in the oral, maxillofacial, neck, and upper limb regions is a refractory neuropathic pain and severely affects the quality of life of patients. Because of the absence of ideal treatments for this condition, relieving pain in the acute stage and preventing the occurrence of PHN are of great clinical significance. However, the optimal intervention for this acute herpetic neuralgia remains obscure. ⋯ Bipolar high-voltage PRF treatment targeting the cervical sympathetic chain could effectively relieve acute herpetic neuralgia in the oral, maxillofacial, neck, and upper limb regions and reduce PHN incidence. The efficacy and safety of this novel treatment make it worthy of recommendation for clinical application.