Neuropathic plasticity

The transmission of signals to the cell body from injured axons induces significant alterations in primary sensory neurons located in the ganglion tissue, the site of the perikaryon of the affected nerve fibers. Disruption of the continuity between the proximal and distal ends leads to substantial adaptability in ganglion cells and induces macrophage-like activity in the satellite cells. Research findings have demonstrated the plasticity of satellite cells following injury. Satellite cells work together with sensory neurons to extend the interconnected surface area in order to permit effective communication...

Experimental studies have shown that neuropathic pain impairs hippocampal synaptic plasticity. Here, we sought to determine the underlying mechanisms responsible for synaptic changes in neuropathic painful mouse hippocampal neurons. Beyond demonstrating proof-of-concept for the location of DExH-box helicase 9 (DHX9) in the nucleus, we found that it did exist in the cytoplasm and DHX9 depletion resulted in structural and functional changes at synapses in the hippocampus. A decrease of DHX9 was observed in the hippocampus after peripheral nerve injury; overexpression of DHX9 in the hippocampus significantly alleviated the nociceptive responses and improved anxiety behaviors...

Epigenetics is a biological process that modifies and regulates gene expression, affects neuronal function, and contributes to pain. However, the mechanism by which epigenetics facilitates and maintains chronic pain is poorly understood. We aimed to determine whether N6-methyladenosine (m6A) specifically modified by methyltransferase 14 (METTL14) alters neuronal activity and governs pain by sensitizing the GluN2A subunit of the N-methyl-D-aspartate receptor (NMDAR) in the dorsal root ganglion (DRG) neurons in a model of chemotherapy-induced neuropathic pain (CINP)...

Pain is a sensory state resulting from complex integration of peripheral nociceptive inputs and central processing. Pain consists of adaptive pain that is acute and beneficial for healing and maladaptive pain that is often persistent and pathological. Pain is indeed heterogeneous, and can be expressed as nociceptive, inflammatory, or neuropathic in nature. Neuropathic pain is an example of maladaptive pain that occurs after spinal cord injury (SCI), which triggers a wide range of neural plasticity. The nociceptive processing that underlies pain hypersensitivity is well-studied in the spinal cord...

Acupuncture is a traditional medicinal practice in China that has been increasingly recognized in other countries in recent decades. Notably, several reports have demonstrated that acupuncture can effectively aid in pain management. However, the analgesic mechanisms through which acupuncture provides such benefits remain poorly understood. Purinergic signaling, which is mediated by purine nucleotides and purinergic receptors, has been proposed to play a central role in acupuncture analgesia. On the one hand, acupuncture affects the transmission of nociception by increasing adenosine triphosphate dephosphorylation and thereby decreasing downstream P2X3, P2X4, and P2X7 receptors signaling activity, regulating the levels of inflammatory factors, neurotrophic factors, and synapsin I...

BACKGROUND: Metformin has been shown to have potent analgesic effects; however, the underlying mechanism of synaptic plasticity mediating analgesia remained ambiguous. METHODS: In this study, animal behavioral tests, whole-cell patch‑clamp recording, immunofluorescence staining, and network pharmacology techniques were applied to elucidate the mechanisms and potential targets of metformin-induced analgesia. RESULTS: Single or consecutive injections of metformin significantly inhibited spinal nerve ligation (SNL)-induced neuropathic pain, and formalin-induced acute inflammatory pain...

PURPOSE: To objectively evaluate the subjective symptoms and characteristics of chronic orbital pain as well as to quantify sensitization of peripheral trigeminal nerves. METHODS: In this prospective cohort study, patients who previously showed a response to peripheral trigeminal nerve blocks for unilateral, idiopathic chronic orbital pain and healthy subjects completed validated questionnaires assessing headaches, neuropathic signs and symptoms, photophobia, and pain qualities...

OBJECTIVE: Cognitive dysfunction is a common comorbidity in patients with chronic pain. Activation of Liver X receptors (LXRs) plays a potential role in improving cognitive disorders in central nervous diseases. In this study, we investigated the role of LXRs in cognitive deficits induced by neuropathic pain. METHODS: We established the spared nerve injury (SNI) model to investigate pain-induced memory dysfunction. Pharmacological activation of LXRs with T0901317 or inhibition with GSK2033 was applied...

Central neuropathic pain arises from a lesion or disease of the central somatosensory nervous system such as brain injury, spinal cord injury, stroke, multiple sclerosis or related neuroinflammatory conditions. The incidence of central neuropathic pain differs based on its underlying cause. Individuals with spinal cord injury are at the highest risk; however, central post-stroke pain is the most prevalent form of central neuropathic pain worldwide. The mechanisms that underlie central neuropathic pain are not fully understood, but the pathophysiology likely involves intricate interactions and maladaptive plasticity within spinal circuits and brain circuits associated with nociception and antinociception coupled with neuronal hyperexcitability...

The dorsal raphe nucleus (DRN) is an important nucleus in pain regulation. However, the underlying neural pathway and the function of specific cell types remain unclear. Here, we report a previously unrecognized ascending facilitation pathway, the DRN to mesoaccumbal dopamine (DA) circuit, for regulating pain. Chronic pain increased the activity of DRN glutamatergic, but not serotonergic, neurons projecting to the ventral tegmental area (VTA) (DRNGlu -VTA) in male mice. Optogenetic activation of DRNGlu -VTA circuit induced a pain-like response in naïve male mice and its inhibition produced analgesic effect in male mice with neuropathic pain...

While neural oscillations play a critical role in sensory perception, it remains unclear how these rhythms function under conditions of neuropathic allodynia. Recent studies demonstrated that the anterior cingulate cortex (ACC) is associated with the affective-aversive component of pain, and plasticity changes in this region are closely linked to abnormal allodynic sensations. Here, to study the mechanisms of allodynia, we recorded local field potentials (LFPs) in the bilateral ACC of awake-behaving rats and compared the spectral power and center frequency of brain oscillations between healthy and CCI (chronic constriction injury) induced neuropathic pain conditions...

BACKGROUND AND PURPOSE: Neuropathic pain affects millions of patients but there are currently few viable therapeutic options available. Microtubule affinity-regulating kinases (MARKs) regulate the dynamics of microtubules and participate in synaptic remodeling. It is unclear whether these changes are involved in the central sensitization of neuropathic pain. This study examined the role of MARK1 or MARK2 in regulating neurosynaptic plasticity induced by neuropathic pain. EXPERIMENTAL APPROACH: A rat spinal nerve ligation (SNL) model was established to induce neuropathic pain...

Pain within the trigeminal system, particularly dental pain, is poorly understood. This study aimed to determine whether single or multiple dental pulp injuries induce persistent pain, its association with trigeminal central nociceptive pathways and whether electroacupuncture (EA) provides prolonged analgesic and neuroprotective effects in a persistent dental pain model. Models of single dental pulp injury (SDPI) and multiple dental pulp injuries (MDPI) were used to induce trigeminal neuropathic pain. The signs of dental pain-related behavior were assessed using the mechanical head withdrawal threshold (HWT)...

Spinal cord injury (SCI) is a debilitating neurological condition that often leads to central neuropathic pain (CNP). As the fundamental mechanism of CNP is not fully established, its management is one of the most challenging problems among people with SCI. In order to shed more light on CNP mechanisms, the aim of the current study was to compare the brain structure between individuals with SCI and CNP and those without CNP by examining the grey-matter volume and the white-matter integrity. Fifty-two individuals with SCI; 28 with CNP and 24 without CNP, underwent an MRI session, including a T1-weighted scan for voxel-based morphometry, and a diffusion-weighted imaging scan for white-matter integrity analysis, as measured by fractional anisotropy and mean diffusivity...

PURPOSE OF REVIEW: While MESS has historically influenced limb salvage versus amputation decisions, its universal applicability remains uncertain. With trauma systems expanding and advancements in trauma care, the need for a nuanced understanding of limb salvage has become paramount. RECENT FINDINGS: Recent literature reflects a shift in the management of mangled extremities. Vascular surgery, plastic surgery, and technological advancements have garnered attention...

Identifying novel therapeutic approaches to promote recovery of neurological functions following spinal cord injury (SCI) remains a great unmet need. Nociceptive signaling in the acute phase of SCI has been shown to inhibit recovery of locomotor function and promote the development of chronic neuropathic pain. We therefore hypothesized that inhibition of nociceptive signaling in the acute phase of SCI might improve long-term functional outcomes in the chronic phase of injury. To test this hypothesis, we took advantage of a selective strategy utilizing AAV6 to deliver inhibitory (hM4Di) DREADDs to nociceptors of the L4-L6 dorsal root ganglia, in order to evaluate the effects of transient nociceptor silencing on long-term sensory and motor functional outcomes in a rat thoracic contusion SCI model...

UNLABELLED: The transition from acute to chronic pain involves maladaptive plasticity in central nociceptive pathways. Growing evidence suggests that changes within the parabrachial nucleus (PBN), an important component of the spino-parabrachio-amygdaloid pain pathway, are key contributors to the development and maintenance of chronic pain. In animal models of chronic pain, PBN neurons become sensitive to normally innocuous stimuli and responses to noxious stimuli become amplified and more often produce after-discharges that outlast the stimulus...

Spasticity is a chronic neurological complication associated with spinal cord injury (SCI), characterized by increased muscle tone and stiffness. A physiological sign of spasticity is hyperreflexia, evident by the loss of evoked rate-dependent depression (RDD) in the monosynaptic spinal circuit, i.e., H-reflex. Although previous work has shown that SCI-induced astrogliosis contributes to hyperexcitability disorders, including neuropathic pain and spasticity, it is unclear how reactive astrocytes can modulate synaptic transmission within the injured spinal cord...

The chemokine fractalkine (FKN, CX3 CL1), a member of the CX3 C subfamily, contributes to neuron-glia interaction and the regulation of microglial cell activation. Fractalkine is expressed by neurons as a membrane-bound protein (mCX3 CL1) that can be cleaved by extracellular proteases generating several sCX3 CL1 forms. sCX3 CL1, containing the chemokine domain, and mCX3 CL1 have high affinity by their unique receptor (CX3 CR1) which, physiologically, is only found in microglia, a resident immune cell of the CNS...

In recent years, the understanding of the mechanisms of acupuncture in the treatment of neurological disorders has deepened, and considerable progress has been made in basic and clinical research on acupuncture, but the relationship between acupuncture treatment mechanisms and brain-derived neurotrophic factor (BDNF) has not yet been elucidated. A wealth of evidence has shown that acupuncture exhibits a dual regulatory function of activating or inhibiting different BDNF pathways. This review focuses on recent research advances on the effect of acupuncture on BDNF and downstream signaling pathways in several neurological disorders...