Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system and is characterized by the destruction of myelin, an insulating lipo-protein layer that forms a sheath around neurons to enhance nervous system signaling. Given the promising characterization of the MMP-9, MBP, and Anti-MBPCP immunoglobulin axis in animal studies modeling multiple sclerosis, this report aims to examine whether this neuropathic process is similar in human studies of multiple sclerosis. This is the first clinical study to explore the possibility of quantifying novel biomarkers to characterize the pain profle of patients with painful conditions such as in MS. In this report, we are able to demonstrate that patients with clinically diagnosed MS do indeed have an increase in anti-MBPCP IgM and IgG in their serum and that the same patients have increased pain profiles when compared to the healthy volunteer control. Based on our results, we believe Anti-MBPCP immunoglobulins may represent one biomarker of clinical neuropathic pain in MS. Ultimately, exploring the relationship between the MMP-9, MBP, and Anti-MBPCP auto-antibodies and MS-associated clinical pain will provide novel diagnostic and therapeutic targets.

Complex orofacial pain disorders, such as trigeminal neuralgia (TN) and atypical facial pain (AFP), can be excruciating and debilitating during attacks. Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, is a powerful analgesic that has been used to treat various chronic pain conditions, but its role in treating complex facial pain has only been recently explored. In this retrospective case series, we reviewed the efficacy of continuous ketamine infusion for 12 patients with facial pain refractory to medical treatment. Patients who presented with a diagnosis of TN were more likely to have significant and sustained pain relief after receiving ketamine infusion. By contrast, those who did not respond to the treatment were more likely to have a diagnosis of AFP. The current report suggests a fundamental difference between these two facial pain disorders in their respective underlying pathophysiology and supports the use of continuous ketamine infusion for refractory TN, but not AFP.

Background

It remains unknown whether continuous or scheduled intermittent bolus local anesthetic administration is preferable for transversus abdominis plane (TAP) catheters. We therefore tested the hypothesis that when using TAP catheters, providing local anesthetic in repeated bolus doses increases the cephalad-caudad cutaneous effects compared with a basal-only infusion.

Methods

Bilateral TAP catheters (posterior approach) were inserted in 24 healthy volunteers followed by ropivacaine 2 mg/mL administration for a total of 6 hours. The right side was randomly assigned to either a basal infusion (8 mL/h) or bolus doses (24 mL administered every 3 hours for a total of 2 bolus doses) in a double-masked manner. The left side received the alternate treatment. The primary end point was the extent of sensory deficit as measured by cool roller along the axillary line at hour 6 (6 hours after the local anesthetic administration was initiated). Secondary end points included the extent of sensory deficit as measured by cool roller and Von Frey filaments along the axillary line and along a transverse line at the level of the anterior superior iliac spine at hours 0 to 6.

Results

Although there were statistically significant differences between treatments within the earlier part of the administration period, by hour 6 the difference in extent of sensory deficit to cold failed to reach statistical significance along the axillary line (mean = 0.9 cm; SD = 6.8; 95% confidence interval -2.0 to 3.8; P = .515) and transverse line (mean = 2.5 cm; SD = 10.1; 95% confidence interval -1.8 to 6.8; P = .244). Although the difference between treatments was statistically significant at various early time points for the horizontal, vertical, and estimated area measurements of both cold and mechanical pressure sensory deficits, no comparison remained statistically significant by hour 6.

Conclusions

No evidence was found in this study involving healthy volunteers to support the hypothesis that changing the local anesthetic administration technique (continuous basal versus hourly bolus) when using ropivacaine 0.2% and TAP catheters at 8 mL/h and 24 mL every 3 hours significantly influences the cutaneous effects after 6 hours of administration. Additional research is required to determine whether changing variables (eg, local anesthetic concentration, basal infusion rate, bolus dose volume, and/or interval) would provide different results.

The corneal epithelium is renowned for high regenerative potential, which is dependent on the coordinated function of its diverse progenitor subpopulations. However, the molecular pathways governing corneal epithelial progenitor differentiation are incompletely understood. Here, we identify a highly proliferative limbal epithelial progenitor subpopulation characterized by expression of basal cell adhesion molecule (BCAM) that is capable of holocone formation and corneal epithelial sheet generation. BCAM-positive cells can be found among ABCB5-positive limbal stem cells (LSCs) as well as among ABCB5-negative limbal epithelial cell populations. Mechanistically, we show that BCAM is functionally required for cellular migration and differentiation and that its expression is regulated by the transcription factor p63. In aggregate, our study identifies limbal BCAM expression as a marker of highly proliferative corneal epithelial progenitor cells and defines the role of BCAM as a critical molecular mediator of corneal epithelial differentiation.