Central post-stroke pain (CPSP) manifests as persistent or intermittent pain following cerebral infarction or hemorrhage and is described as "one of the most agonizing, disabling, and refractory pain syndromes." Its treatment represents a significant clinical challenge. In this case, we used transcranial low-intensity focused ultrasound (tLIFU), an emerging non-invasive neuromodulation approach distinct from pharmacological and traditional neuromodulation methods, to treat CPSP patients, achieving satisfactory outcomes. This approach may inspire new perspectives on innovative pain management. A 66-year-old male veteran suffered long-term CPSP, with unsatisfactory pain relief from previous paregoric interventions, including transcranial magnetic stimulation (TMS). Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) revealed abnormal activity in a region of interest (ROI) that responded to analgesic medication adjustments. This ROI was anatomically consistent with the cingulum bundle. Given this finding, we used tLIFU to demonstrate deep stimulation of the ROI. Remarkable pain reduction was observed after 1 week of tLIFU neuromodulation, allowing for a slight tapering of the gabapentin dose. The analgesic effects of tLIFU were sustained throughout a 5-month follow-up period, with no adverse events reported. Since day 120, the patient has remained off analgesic medications, and at the 150-day follow-up, BOLD-fMRI revealed a normalized activity pattern in the region of interest (ROI). Additionally, significant clinical improvement was noted in the patient's emotional state. This case report highlights the potential of tLIFU technology to expand therapeutic options in clinical pain management. Exploratory research into the clinical efficacy and the underlying mechanisms of tLIFU in pain treatment may contribute to a deeper understanding of pain pathogenesis and support the development of novel therapeutic strategies.

Thalamic hemorrhage (TH), a critical subtype of intracerebral hemorrhage, often leads to central post-stroke pain (CPSP) and neurological deficits, yet its molecular mechanisms remain poorly understood. This study investigated the role of Rip3 in TH pathophysiology by constructing Rip3-knockout (KO) mice and integrating behavioral assessments, transcriptomic sequencing, and molecular experiments. Results demonstrated that TH induced motor dysfunction, mechanical pain hypersensitivity, working memory impairment, and anxiety-like behaviors in wild-type (WT) mice, while Rip3 knockout significantly alleviated pain sensitivity and anxiety and reduced hemorrhage volume. Transcriptomic analysis identified 956 Rip3-related candidate genes, among which Tac1, Gal, and Pdyn were validated as key downstream genes through protein-protein interaction networks and experimental assays. RT-qPCR and Western blot revealed significant upregulation of these genes in WT mice post-TH, with reduced expression in KO mice. Functional enrichment analysis implicated these genes in pathways such as NEUREXINS_AND_NEUROLIGINS and DOPAMINERGIC_NEUROGENESIS. Drug prediction identified potential therapeutic candidates, including Nizatidine, Ginger Allergenic Extract, Paregoric, and Estradiol 3-Benzoate, with the latter showing promise in modulating synaptic plasticity and pain signaling. Inhibition of Pdyn and Tac1 alleviated mechanical allodynia, while all three inhibitors, including Gal's, exhibited significant anxiolytic effects in the TH-induced CPSP model. This study reveals, for the first time, a correlative link between Rip3 and post-TH neurological injury and CPSP, potentially mediated via Tac1, Gal, and Pdyn regulation, providing novel targets for therapeutic intervention. Future research should validate direct Rip3-gene interactions and the efficacy of predicted drugs.

Glycyrrhizae Radix et Rhizoma, a traditional Chinese medicine also known as Gan Cao (GC), is frequently included in clinical prescriptions for the treatment of pneumonia. However, the pharmacological components of GC for pneumonia treatment are rarely explored. Gan An He Ji oral liquid (GAHJ) has a simple composition and contains GC liquid extracts and paregoric, and has been used clinically for many years. Therefore, GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia. We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days. Using the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo, we obtained 168 related components of GC in humans, consisting of 24 prototype components and 144 metabolites, with 135 compounds screened in plasma and 82 in urine. After analysis of the metabolic transformation relationship and relative exposure, six components (liquiritin, liquiritigenin, glycyrrhizin, glycyrrhetinic acid, daidzin, and formononetin) were selected as potential effective components. The experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase (iNOS). Interestingly, glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo. The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS. Thus, the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

Ten patients with parapharyngeal space tumor, all underwent surgery, which of two cases concurrent FBS，analyze its clinical characteristics and review the related literatures. Two cases complicated with FBS, both with primary healing of incision, the pathological diagnosis are pleomorphic adenoma and schwannoglioma respectively, both give non-steroidal anti-inflammatory drugs, paregoric and anticonvulsants, followed up for nine months and 16 months respectively, both two cases partial relief. FBS is one of surgical complications of parapharyngeal space，which should not be neglected by physicians. Additional investigations of FBS are needed to gain a better understanding of the pathophysiological mechanisms of this condition.

The incidence of neonatal abstinence syndrome (NAS) has increased dramatically during the past 15 years, likely due to an increase in antepartum maternal opiate use. Optimal care of these patients is still controversial because of the available published literature lacking sufficient sample size, placebo control, and comparative pharmacologic trials. Primary treatment for NAS consists of opioid replacement therapy with either morphine or methadone. Paregoric and tincture of opium have been abandoned because of relative safety concerns. Buprenorphine is emerging as a treatment option with promising initial experience. Adjunctive agents should be considered for infants failing treatment with opioid monotherapy. Traditionally, phenobarbital has been used as adjunctive therapy; however, results of clonidine as adjunctive therapy for NAS appear to be beneficial. Future directions for research in NAS should include validating a simplified scoring tool, conducting comparative studies, exploring home management options, and optimizing management through pharmacogenomics.

Although a statement on Neonatal Drug Withdrawal was published in 1998 by the American Academy of Pediatrics, pharmacologic management of neonatal abstinence syndrome (NAS) remains a challenge. Published clinical trials are limited, restricting treatment decision making to practitioner's experience and preference rather than evidence-based medicine. To optimize withdrawal symptom prevention, drug selection is often based on the offending agent (opioids versus polysubstance exposure), clinical presentation, mechanism of action (agonist versus partial agonist/antagonist, receptor effects), pharmacokinetic parameters and available drug formulations. This review addresses risk factors and pathophysiology of NAS, summarizes parameters of common drugs used for the management of NAS, and reviews published literature of standard therapies as well as newer agents. Based on the current literature, paregoric is no longer recommended and oral morphine solutions remain the mainstay of therapy for opiate withdrawal. Other potential therapies include methadone, buprenorphine, phenobarbital and clonidine with the latter two agents as adjunctive therapies.

A liquid alcoholic extract of Papaver somniferum named Elixir Paregorico is extensively used for diarrheal diseases in Brazil. Its increased popularity has brought concerns and fears over the safety of this herbal product. Given the lack of investigative clinical studies, in this regard, this study investigated whether Elixir Paregorico administration causes any noticeable toxic effects in healthy volunteers. In all, 28 middle-aged healthy male (n = 14) and female (n = 14) were enrolled. After screening and a washout period, eligible subjects received four oral doses per day of Elixir Paregorico (3 mL diluted in 30 mL of water) over a 10-day period. Altogether, all 28 participants completed the study. The results of hematological and biochemical tests performed pre and post-treatment were within the normal range. In both male and female volunteers, there were no statistical differences (P > 0.05) in the results of clinical and laboratory tests performed at screening, on 5th and 10th day visits, and at final assessment. Although mild adverse events were related, which subsided spontaneously, no serious untoward reactions were reported following Elixir Paregorico administration. To our knowledge, this is the first demonstration that Elixir Paregorico administered four times a day for 10 days is safe and does not cause any noticeable toxic effect in healthy volunteers.

Paregoric elixir is a phytomedicinal product which is used widely as an analgesic, antispasmodic and antidiarrheal agent. Here, we investigated the pharmacological actions and some of the mechanisms of action of paregoric elixir and compared its action with some of its components, the alkaloids morphine and papaverine. The paregoric elixir given orally to mice did not present relevant toxic effects, even when administered in doses up to 2000-fold higher than those used clinically. However, it showed an antinociceptive action that was more potent, but less efficacious, than morphine. In contrast to morphine, its effect was not dose-dependent and not reversed by the non-selective opioid antagonist naloxone. Moreover, paregoric elixir produced tolerance, but did not cause cross-tolerance, with the antinociceptive actions of morphine. When assessed in the gastrointestinal motility in vivo, paregoric elixir elicited graduated reduction of gastrointestinal transit. Finally, like morphine and papaverine, paregoric elixir concentration-dependently inhibited electrically-induced contraction of the guinea pig isolated ileum. In vivo and in vitro gastrointestinal actions of paregoric elixir were not reversed by naloxone. Collectively, the present findings lead us to suggest that the pharmacological actions produced by paregoric elixir are probably due to a synergic action of its constituents.

Neonatal opioid withdrawal often requires treatment but there have been few recent studies of current pharmacological interventions to guide treatment. This retrospective chart review provides an exploratory examination of newborns treated with either methadone or paregoric for opioid withdrawal and outlines dosage ranges and intervals, side effects, and clinical outcomes of the two regimens. The outcome variables examined were time to resolution of withdrawal symptoms, rate of decrease in symptom severity, and length of hospital stay. There were no observed differences in outcome variables between the two treatment groups and side effect profiles were similar. Dosages, dosage intervals, and tapering regimens were consistent with American Academy of Pediatrics recommendations. Although the sample size is small and standardized regimens were not used, this study provides preliminary data about dosing levels and dosing intervals of these two pharmacologic treatment agents. Both groups of infants had favorable outcomes, although given the variation in treatment regimens it is difficult to draw an equation of equivalency. These results are applicable to the design of future studies of pharmacological interventions.