Accepted

Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.

On the slow path to improving the life expectancy and quality of life of patients post spinal cord injury (SCI), recovery remains controversial. The potential role of the regenerative capacity of the nervous system has led to numerous attempts to stimulate the SCI to re-establish the interrupted sensorimotor loop and to understand its potential in the recovery process. Numerous resources are now available, from pharmacological to biomolecular approaches and from neuromodulation to sensorimotor rehabilitation interventions based on the use of various neural interfaces, exoskeletons, and virtual reality applications. The integration of existing resources seems to be a promising field of research, especially from the perspective of improving living conditions in the short to medium term. Goals such as reducing chronic forms of neuropathic pain, regaining control over certain physiological activities, and enhancing residual abilities are often more urgent than complete functional recovery. In this perspective article, we provide an overview of the latest interventions for the treatment of SCI through broad phases of injury rehabilitation. The underlying intention of this work is to introduce a spinal cord neuroplasticity-based multimodal approach to promote functional recovery and improve quality of life after SCI. Nonetheless, when used separately, biomolecular therapeutic approaches have been shown to have modest outcomes.

Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a patient's quality of life. In addition, endometriosis imposes an immense financial burden on the healthcare system. At present, laparoscopy is the gold standard for diagnosing the disease because other non-invasive diagnostic tests have less accuracy. In addition, other diagnostic tests have low accuracy. Therefore, there is an urgent need for the development of a highly sensitive, more specific, and non-invasive test for the early diagnosis of endometriosis. Numerous researchers have suggested miRNAs as potential biomarkers for endometriosis diagnosis due to their specificity and stability. However, the greatest prognostic force is the determination of several miRNAs, the expression of which varies in a given disease. Despite the identification of several miRNAs, the studies are investigatory in nature, and there is no consensus on them. In the present review, we first provide an introduction to the dysregulation of miRNAs in patients with endometriosis and the potential use of miRNAs as biomarkers in the detection of endometriosis. Then we will describe the role of the mir-200 family in endometriosis. Several studies have shown that the expression of the mir-200 family changes in endometriosis patients, suggesting that they could be used as a diagnostic biomarker and therapeutic target for endometriosis.

Bone cancer pain (BCP) is a clinically intractable mixed pain, involving inflammation and neuropathic pain, and its mechanisms remain unclear. CXC chemokine receptor 1 (CXCR1, IL-8RA) and 2 (CXCR2, IL-8RB) are high-affinity receptors for interleukin 8 (IL8). According to previous studies, CXCR2 plays a crucial role in BCP between astrocytes and neurons, while the role of CXCR1 remains unclear. The objective of this study was to investigate the role of CXCR1 in BCP. We found that CXCR1 expression increased in the spinal dorsal horn. Intrathecal injection of CXCR1 siRNA effectively attenuated mechanical allodynia and pain-related behaviors in rats. It was found that CXCR1 was predominantly co-localized with neurons. Intrathecal injection of CXCR1-siRNA reduced phosphorylated JAK2/STAT3 protein levels and the NLRP3 inflammasome (NLRP3, caspase1, and IL-1β) levels. Furthermore, in vitro cytological experiments confirmed this conclusion. The study results suggest that the spinal chemokine receptor CXCR1 activation mediates BCP through JAK2/STAT3 signaling pathway and NLRP3 inflammasome (NLRP3, caspase1, and IL-1β).

Degeneration of the intervertebral disc (IVD) is a major contributor to low back pain (LBP). IVD degeneration is characterized by abnormal production of inflammatory cytokines secreted by IVD cells. Although the underlying molecular mechanisms of LBP have not been elucidated, increasing evidence suggests that LBP is associated particularly with microglia in IVD tissues and the peridiscal space, aggravating the cascade of degenerative events. In this study, we implemented our microfluidic chemotaxis platform to investigate microglial inflammation in response to our reconstituted degenerative IVD models. The IVD models were constructed by stimulating human nucleus pulposus (NP) cells with interleukin-1β and producing interleukin-6 (129.93 folds), interleukin-8 (18.31 folds), C-C motif chemokine ligand-2 (CCL-2) (6.12 folds), and CCL-5 (5.68 folds). We measured microglial chemotaxis ( < 0.05) toward the conditioned media of the IVD models. In addition, we observed considerable activation of neurodegenerative and deactivation of protective microglia via upregulated expression of CD11b ( < 0.001) and down-regulation of CD206 protein ( < 0.001) by soluble factors from IVD models. This, in turn, enhances the inflammatory milieu in IVD tissues, causing matrix degradation and cellular damage. Our findings indicate that degenerative IVD may induce degenerative microglial proinflammation, leading to LBP development.