Accepted

Keratoneuralgia, a clinical diagnosis of sensitized corneal pain without visible ocular surface damage, generally has minimal response to conventional therapies. Causes include refractive surgery and chronic dry eye. We evaluated the efficacy of Plasma Rich in Growth Factors (PRGF), a novel treatment prepared using a commercially available kit, in patients with keratoneuralgia. A retrospective chart review identified patients who had the clinical diagnosis of keratoneuralgia and were treated with PRGF for at least 3 months from October 2015 to April 2020 at a single academic institution. Both objective eye exam findings and concurrent treatments were obtained at baseline, 3 months, and final visit (if available). A questionnaire was administered to identified patients, including symptoms scores measured with a visual analog scale. The results of this survey and other objective findings were compared before and after PRGF treatment. 16 out of 32 patients (50%) with a mean follow-up period of 33 ± 26 months answered the questionnaire. Refractive surgeries were the cause of keratoneuralgia in 14 patients (87.5%), with LASIK the most common procedure (11 patients, 69%). There were no adverse events recorded or reported. Symptom scored by VAS in a modified Symptoms Assessment in Dry Eye questionnaire significantly decreased after PRGF use (85 ± 16 to 45 ± 33, = 0.0002). Ten patients (63%) reported PRGF is superior to other therapy and would recommend to others. There were no significant trends in visual acuity, objective exam findings, or concurrent treatments after PRGF treatment. PRGF is safe and can potentially alleviate symptoms in patients with keratoneuralgia, a rare but devastating complication after refractive surgery. Prospective trial is indicated to explore PRGF as a potentially useful treatment for keratoneuralgia.

White matter hyperintensities (WMHs) have been observed with greater frequency in patients with migraine and are thought to be associated with impaired cognition and function. The relationship between WMHs and right-to-left shunt (RLS) in migraine patients is unknown. We performed a systematic review to determine if there is an association between RLS and WMHs in patients with migraine.

The descending pain modulatory pathway exerts important bidirectional control of nociceptive inputs to dampen and/or facilitate the perception of pain. The ventrolateral periaqueductal gray (vlPAG) integrates inputs from many regions associated with the processing of nociceptive, cognitive, and affective components of pain perception, and is a key brain area for opioid action. Opioid receptors are expressed on a subset of vlPAG neurons, as well as on both GABAergic and glutamatergic presynaptic terminals that impinge on vlPAG neurons. Microinjection of opioids into the vlPAG produces analgesia and microinjection of the opioid receptor antagonist naloxone blocks stimulation-mediated analgesia, highlighting the role of endogenous opioid release within this region in the modulation of nociception. Endogenous opioid effects within the vlPAG are complex and likely dependent on specific neuronal circuits activated by acute and chronic pain stimuli. This review is focused on the cellular heterogeneity within vlPAG circuits and highlights gaps in our understanding of endogenous opioid regulation of the descending pain modulatory circuits.

Functional brain networks and the perception of pain can fluctuate over time. However, how the time-dependent reconfiguration of functional brain networks contributes to chronic pain remains largely unexplained. Here, we explored time-varying changes in brain network integration and segregation during pain over a disease-affected area (joint) compared to a neutral site (thumbnail) in 28 patients with rheumatoid arthritis (RA) in comparison with 22 healthy controls (HC). During functional magnetic resonance imaging, all subjects received individually calibrated pain pressures corresponding to visual analog scale 50 mm at joint and thumbnail. We implemented a novel approach to track changes of task-based network connectivity over time. Within this framework, we quantified measures of integration (participation coefficient, PC) and segregation (within-module degree -score). Using these network measures at multiple spatial scales, both at the level of single nodes (brain regions) and communities (clusters of nodes), we found that PC at the community level was generally higher in RA patients compared to HC during and after painful pressure over the inflamed joint and corresponding site in HC. This shows that all brain communities integrate more in RA patients than in HC for time points following painful stimulation to a disease-relevant body site. However, the elevated community-related integration seen in patients appeared to not pertain uniquely to painful stimulation at the inflamed joint, but also at the neutral thumbnail, as integration and segregation at the community level did not differ across body sites in patients. Moreover, there was no specific nodal contribution to brain network integration or segregation. Altogether, our findings indicate widespread and persistent changes in network interaction in RA patients compared to HC in response to painful stimulation.

To describe the team approach of an interventional pain management practice, with particular emphasis on advanced practice providers (APPs), in the selection, education, care, and management of peripheral nerve stimulation (PNS) patients.