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Treatment of subacute and chronic heel pain often presents a unique challenge to the physician. Regenerative therapies, such as injectable amnion and connective tissue matrix, may represent a promising new approach in these patients, and have become increasingly popular in the United States. However, little literature exists evaluating these injections compared to conventional nonoperative means. As such, we designed a retrospective comparative study evaluating patients in our practice who received a standardized plantar fascial treatment protocol only (standard therapy), and those who received regenerative plantar fascial injections in addition to standard therapy. A total of 54 patients were followed over a 3-month observation period (91.7 ± 73.9 days), with numeric pain rating (NPR) serving as the primary outcome. Both groups saw an improvement in NPR at the end of the observation period, but patients in the regenerative therapy group demonstrated lower pain scores than those receiving standard therapy alone (mean NPR 2.1 ± 2.3 vs 4.4 ± 2.8, p = .004). Additionally, those in the standard therapy group were significantly more likely to proceed onto surgical intervention compared to the regenerative therapy group (unadjusted odds ratio 15.6, 95% CI 3.0-27.9). The use of regenerative injections for subacute and chronic plantar fasciitis showed promise in our study, and may help mitigate against the need for invasive surgical intervention.

Epidemiological research has found that between 5 and 12 percent of the population suffers from chronic rhinosinusitis. Patients are dealing with local side effects such as nasal dryness, sporadic sneezing, and nasal pain in addition to the inflammation. The aim of this study was to synthesize a polymer based on hyaluronic acid in order to provide lubrication combined with a ligand leading to a covalent binding on the nasal mucosa. Hyaluronic acid (HA) was modified with L-cysteine ethyl ester hydrochloride (CYS) via amid bond formation. Ellman's assay, together with spectroscopic techniques like IR and H NMR, confirmed that HACys had been successfully synthesized. It was demonstrated that HACys is safe for administration on the nasal mucosa. The mucoadhesive potential was determined by 3.26-fold with the rotating cylinder assay and 1.4-fold in terms of bioadhesive examination, respectively. Further, the stability of the modified polymer was improved by 7.6-fold compared to the unmodified polymer. Spraying the formulation on the nasal mucosa, the residence time of a model drug was 1.74-fold prolonged at the site of action compared to unmodified polymer. In light of these findings, modified hyaluronic acid (HACys) displayed compelling properties such as lubricity, targeted application, long-lasting effect, and safety and therefore could be an excellent candidate for nasal application.

ARNSTEN, A.F.T., M.K.P. Joyce and A.C. Roberts. The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion. NEUROSCI BIOBEHAV REV XXX-XXX, 2022. The symptoms of major-depressive-disorder include psychic pain and anhedonia, i.e. seeing the world through an "aversive lens". The neurobiology underlying this shift in worldview is emerging. Here these data are reviewed, focusing on how activation of subgenual cingulate (BA25) induces an "aversive lens", and how higher prefrontal cortical (PFC) areas (BA46/10/32) provide top-down regulation of BA25 but are weakened by excessive dopamine and norepinephrine release during stress exposure, and dendritic spine loss with chronic stress exposure. These changes may generate an attractor state, which maintains the brain under the control of BA25, requiring medication or neuromodulatory treatments to return connectivity to a more flexible state. In line with this hypothesis, effective anti-depressant treatments reduce the activity of BA25 and restore top-down regulation by higher circuits, e.g. as seen with SSRI medications, ketamine, deep brain stimulation of BA25, or rTMS to strengthen dorsolateral PFC. This research has special relevance in an era of chronic stress caused by the COVID19 pandemic, political unrest and threat of climate change.

Recent studies have shown that the ephrin/Eph signaling pathway may contribute to the pathology of neuropathic pain. Drugs like progesterone may be used to counteract both thermal hyperalgesia and mechanical allodynia in different models of neuropathic pain. The present study was designed to determine progesterone's modulatory role on neuropathic pain and spinal expression of ephrin-B2 following chronic constriction nerve injury (CCI). Thirty-six adult male Wistar rats were used. The sciatic nerve was chronically constricted. Progesterone (5 mg/kg and 15 mg/kg) was administrated for 10 days (from day 1 up to day10) following sciatic constriction. Behavioral tests were performed before surgery (day 0) and on days 1, 3, 7, and 14 after CCI and before progesterone administration on the same days. Western blotting was performed on days 3, 7, and 14 post-surgery. The findings showed that after CCI, the expression of spinal cord ephrin-B2 increased significantly in parallel with mechanical allodynia and thermal hyperalgesia. Post-injury administration of progesterone (15 mg/kg but not 5) decreased mechanical allodynia, thermal hyperalgesia, and the expression of spinal ephrin-B2. It is concluded that post-injury repeated administration of progesterone could be an effective way of alleviating neuropathic pain by suppressing ephrin-B2 activation and helps to make the better design of steroid-based therapies to inhibit pain after peripheral injury.

The seed of the African walnut, Plukenetia conophora Mull.-Arg is well-known for its nutritional and medicinal values. The seed oil is widely used in massages to relieve pain, as nerve tonic and to enhance sexual performance.

Scutellaria baicalensis (SB) is a traditional Chinese medicine (TCM). In the clinical application of TCM, SB has been divided into two specifications (Ziqin and Kuqin) for a long time. At present, the Chinese Pharmacopoeia Commission no longer distinguishes between the two. However, the two specifications of medicinal materials and pieces are still in circulation in the market.

Neuropathic pain is a common health problem resulting in exacerbated response to noxious and non noxious stimuli, as well as impaired emotional and cognitive responses. Unfortunately, neuropathic pain is also one of the most difficult pain syndromes to manage, highlighting the importance of better understanding the brain regions and neuromodulatory mechanisms involved in its regulation. Among the many interconnected brain areas which process pain, the amygdala is known to play an important role in the integration of sensory and emotional pain signals. Here we questioned the ability of a recently identified neuromodulatory mechanism associated with the metabotropic glutamate receptors mGlu in the amygdala to modulate neuropathic pain. In a murine model of peripheral mononeuropathy, we demonstrate that pharmacological activation of amygdala mGlu efficiently alleviates sensory and depressive-like symptoms in both male and female mice. Moreover, we reveal a differential modulation of these symptoms. Activating mGlu in the contralateral amygdala relative to the side of the mononeuropathy, is necessary and sufficient to relieve both sensory and depressive-like symptoms, while ipsilateral activation solely reduces depressive-like symptoms. Furthermore, using photopharmacology, a recent strategy allowing precise photocontrol of endogenous proteins, we further demonstrate the dynamic alleviation of neuropathic pain through light-dependent facilitation of mGlu by a photoswitchable positive allosteric modulator. Finally, coupling photopharmacology and analgesic conditioned place preference, we show a significant pain-reducing effect of mGlu4 activation. Taken together, these data highlight the analgesic potential of enhancing amygdala mGlu activity to counteract neuropathy reinforcing its therapeutic interest for the treatment of pathological pain.

This study examined whether pericapsular nerve group (PENG) block combined with local infiltration analgesia (LIA) could improve pain management and functional recovery after total hip arthroplasty (THA).

To assess the risk of new persistent opioid use in opioid-naïve men undergoing male fertility procedures DESIGN: Retrospective cohort study using a claims database SETTING: TriNetX Diamond Network – a database linking electronic medical record data and claims – assessing men undergoing fertility procedure between 2010 and 2021.

Moderate haemophilia has traditionally been associated with less complications than severe haemophilia. Changes in treatment recommendations have highlighted the burden of moderate haemophilia with a subset of patients with a severe bleeding phenotype. The ankle joint is disproportionally affected by ankle haemarthropathy however the impact has not been evaluated in moderate haemophilia, nor the effect on health related quality of life (HRQoL) or foot and ankle outcomes.