Endoplasmic reticulum stress in the dorsal root ganglia regulates large-conductance potassium channels and contributes to pain in a model of multiple sclerosis.

Neuropathic pain is a common symptom of multiple sclerosis (MS) and current treatment options are ineffective. In this study, we investigated whether endoplasmic reticulum (ER) stress in dorsal root ganglia (DRG) contributes to pain hypersensitivity in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Inflammatory cells and increased levels of ER stress markers are evident in post-mortem DRGs from MS patients.

Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion.

Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling.

Voluntary wheel running reveals sex-specific nociceptive factors in murine experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an inflammatory, neurodegenerative autoimmune disease associated with sensory and motor dysfunction. Although estimates vary, ∼50% of patients with MS experience pain during their disease. The mechanisms underlying the development of pain are not fully understood, and no effective treatment for MS-related pain is available.

Manipulation of Neurotransmitter Levels Has Differential Effects on Formalin-Evoked Nociceptive Behavior in Male and Female Mice.

Unlabelled: Changes in serotonin (5-hydroxytryptamine; 5-HT), noradrenaline (NA), and γ-aminobutyric acid (GABA) levels in the spinal cord are known to occur in response to nociceptive stimuli, yet little research has examined possible underlying sex differences in these changes and how they might affect nociception. We have used pharmacological approaches in a well established model of tonic nociception, the formalin test, to explore the effects of altering neurotransmitter levels on nociceptive responses in male and female C57BL/6 mice. The monoamine oxidase (MAO) inhibitor phenelzine (PLZ), its metabolite phenylethylidenehydrazine (PEH), and a derivative compound of PLZ, N(2)-acetylphenelzine (N(2)-AcPLZ), were used to increase endogenous levels of: GABA, 5-HT, and NA (PLZ); GABA alone (PEH); or 5-HT and NA only (N(2)-AcPLZ).

Facial hypersensitivity and trigeminal pathology in mice with experimental autoimmune encephalomyelitis.

Trigeminal neuropathic pain is a well-recognized complication of the demyelinating disease multiple sclerosis (MS). However, the mechanisms underlying MS-related trigeminal neuropathic pain are poorly understood. This can be attributed, at least in part, to the lack of an animal model that exhibits trigeminal pathology similar to that described in MS.