Revolutionizing orofacial pain management: the promising potential of stem cell therapy.

Orofacial pain remains a significant health issue in the United States. Pain originating from the orofacial region can be composed of a complex array of unique target tissue that contributes to the varying success of pain management. Long-term use of analgesic drugs includes adverse effects such as physical dependence, gastrointestinal bleeding, and incomplete efficacy. The use of mesenchymal stem cells for their pain relieving properties has garnered increased attention. In addition to the preclinical and clinical results showing stem cell analgesia in non-orofacial pain, studies have also shown promising results for orofacial pain treatment. Here we discuss the outcomes of mesenchymal stem cell treatment for pain and compare the properties of stem cells from different tissues of origin. We also discuss the mechanism underlying these analgesic/anti-nociceptive properties, including the role of immune cells and the endogenous opioid system. Lastly, advancements in the methods and procedures to treat patients experiencing orofacial pain with mesenchymal stem cells are also discussed.

Sex-dependent differences in the genomic profile of lingual sensory neurons in naïve and tongue-tumor bearing mice.

Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naïve as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: (1) FACS sorting obtained higher number of neurons from female trigeminal ganglia (TG) compared to males; (2) Naïve female neurons innervating the tongue expressed immune cell markers such as Csf1R, C1qa and others, that weren't expressed in males. This was validated by Immunohistochemistry. (3) Accordingly, immune cell markers such as Csf1 exclusively sensitized TRPV1 responses in female TG neurons. (4) Male neurons were more tightly regulated than female neurons upon tumor growth and very few differentially expressed genes (DEGs) overlapped between the sexes, (5) Male DEGs contained higher number of transcription factors whereas female DEGs contained higher number of enzymes, cytokines and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, pathways and molecular function of tongue-innervating sensory neurons.

Sex-dependent Differences in the Genomic Profile of Lingual Sensory Neurons in Naïve and Tongue-Tumor Bearing Mice.

Mechanisms of sex-dependent orofacial pain are widely understudied. A significant gap in knowledge exists about comprehensive regulation of tissue-specific trigeminal sensory neurons in diseased state of both sexes. Using RNA sequencing of FACS sorted retro-labeled sensory neurons innervating tongue tissue, we determined changes in transcriptomic profiles in males and female mice under naïve as well as tongue-tumor bearing conditions Our data revealed the following interesting findings: 1) Tongue tissue of female mice was innervated with higher number of trigeminal neurons compared to males; 2) Naïve female neurons innervating the tongue exclusively expressed immune cell markers such as Csf1R, C1qa and others, that weren't expressed in males. This was validated by Immunohistochemistry. 4) Accordingly, immune cell markers such as Csf1 exclusively sensitized TRPV1 responses in female TG neurons. 3) Male neurons were more tightly regulated than female neurons upon tumor growth and very few differentially expressed genes (DEGs) overlapped between the sexes, 5) Male DEGs contained higher number of transcription factors whereas female DEGs contained higher number of enzymes, cytokines and chemokines. Collectively, this is the first study to characterize the effect of sex as well as of tongue-tumor on global gene expression, pathways and molecular function of tongue-innervating sensory neurons.