Accepted

The prevalence of obesity skyrocketed over the past decades to become a significant public health problem. Obesity is recognized as a low-grade inflammatory disease and is linked with several comorbidities such as diabetes, circulatory disease, common neurodegenerative diseases, as well as chronic pain. Adipocytes are a major neuroendocrine organ that continually, and systemically, releases pro-inflammatory factors. While the exact mechanisms driving obesity-induced pain remain poorly defined, nociceptor hypersensitivity may result from the systemic state of inflammation characteristic of obesity as well as weight surplus-induced mechanical stress. Obesity and pain also share various genetic mutations, lifestyle risk factors, and metabolic pathways. For instance, fat pads are often found hyper-innervated and rich in immune cell types of multiple origins. These immunocytes release cytokines, amplifying nociceptor function, which, in turn, via locally released neuropeptides, sustain immunocytes' function. Here, we posit that along with mechanical stress stemming from extra weight, the local neuro-immune interplay occurring within the fat pads maintains the state of chronic low-grade inflammation and heightens sensory hypersensitivity. Overall, stopping such harmful neuro-immune crosstalk may constitute a novel pathway to prevent obesity-associated comorbidities, including neuronal hypersensitivity.

C-tactile afferents are hypothesized to form a distinct peripheral channel that encodes the affective nature of touch. Prevailing views indicate they project, as with other unmyelinated afferents, in lamina I-spinothalamic pathways that relay homeostatically relevant information from the body toward cortical regions involved in interoceptive processing. However, in a recent study, we found that spinothalamic ablation in humans, while profoundly impairing the canonical spinothalamic modalities of pain, temperature, and itch, had no effect on benchmark psychophysical affective touch metrics. These novel findings appear to indicate that perceptual judgments about the affective nature of touch pleasantness do not depend on the integrity of the lamina I-spinothalamic tract. In this commentary, we further discuss the implications of these unexpected findings. Intuitively, they suggest that signaling of emotionally relevant C-tactile mediated touch occurs in an alternative ascending pathway. However, we also argue that the deficits seen following interruption of a putative C-tactile lamina I-spinothalamic relay might be barely perceptible-a feature that would underline the importance of the C-tactile afferent in neurodevelopment.

Long non-coding RNAs (lncRNAs) are a group of non-coding RNAs longer than 200 nucleotides, which are defined as transcripts. The lncRNAs are involved in regulating gene expression at epigenetic, transcriptional, and post-transcriptional levels. Recent studies have found that lncRNA is closely related to many diseases like neurological diseases, endocrine and metabolic disorders. Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes mellitus. In this review, we highlight the latest research related to lncRNAs in DPN.

Neuropathic pain remains poorly treated, with most new drugs falling through the translational gap. The traditional model of bench-to-bedside research has relied on identifying new mechanisms/targets in animal models and then developing clinical applications. Several have advocated bridging the translational gap by beginning with clinical observations and back-translating to animal models for further investigation of mechanisms. There is good evidence that phenotyping of patients through quantitative sensory testing can lead to improved treatment selection and hence improved patient outcomes. This practice has been widely adopted in clinical investigations, but its application in preclinical research is not mainstream. In this review, we retrospectively examine our historical rodent data sets with the aim of reconsidering drug effects on sensory neuronal endpoints, their alignment with clinical observations, and how these might guide future clinical studies.