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This study observed the cutaneous analgesic effect of adrenergic agonists when combined with lidocaine. We aimed at the usefulness of 4 adrenergic agonists and epinephrine as analgesics or as tools to prolong the effect of local anesthetics using a model of cutaneous trunci muscle reflex (pinprick pain) in rats. We showed that subcutaneous 4 adrenergic agonists and epinephrine, as well as the local anesthetic bupivacaine and lidocaine, developed a concentration-dependent cutaneous analgesia. The rank order of the efficacy of different compounds (ED ; median effective dose) was epinephrine [0.013 (0.012 – 0.014) μmol] > oxymetazoline [0.25 (0.22 – 0.28) μmol] > naphazoline [0.42 (0.34 – 0.53) μmol] = bupivacaine [0.43 (0.37 – 0.50) μmol] > xylometazoline [1.34 (1.25 – 1.45) μmol] > lidocaine [5.86 (5.11 – 6.72) μmol] > tetrahydrozoline [6.76 (6.21 – 7.36) μmol]. The duration of full recovery caused by tetrahydrozoline, oxymetazoline, or xylometazoline was greater (P<0.01) than that induced via epinephrine, bupivacaine, lidocaine, or naphazoline at equianesthetic doses (ED , ED , and ED ). Co-administration of lidocaine (ED ) with 4 adrenergic agonists or epinephrine enhanced the cutaneous analgesic effect. We observed that 4 adrenergic agonists and epinephrine induce analgesia by themselves, and such an effect has a longer duration than local anesthetics. Co-administration of lidocaine with the adrenergic agonist enhances the analgesic effect, and the cutaneous analgesic effect of lidocaine plus naphazoline (or oxymetazoline) is greater than that of lidocaine plus epinephrine.

Migraine is a common neurological disorder characterized by repeated headaches of varying intensity. The prevalence and severity of migraine headaches disproportionally affects women, particularly during the postpartum period. Moreover, migraines during pregnancy have been associated with adverse maternal outcomes, including preeclampsia and postpartum stroke. However, due to the lack of a validated instrument for uniform case ascertainment on postpartum migraine headache, there is uncertainty in the reported prevalence in the literature.

Medication management and cognitive behavioral therapy (CBT) are commonly used treatments for chronic low back pain (CLBP). However, little evidence is available comparing the effectiveness of these approaches.

Cannabinoids are considered a therapeutic option to patients suffering from treatment refractory chronic pain (TRCP) insufficiently relieved by conventional analgesics or experiencing intolerable adverse events (AEs) from those. This study aimed to explore safety and effectiveness of oral cannabinoids among patients with TRCP.

This prospective observational study included 80 adults (>18 years) patients admitted to the intensive care unit who were unconscious (Glasgow Coma Scale [GCS] score < 9 with a motor response < 5) and receiving mechanical ventilation. A tetanic stimulation was used to assess nociception; automated pupillometry (Algiscan, ID-MED, France) was used to compute the pupillary pain index score (PPI), with a PPI > 4 considered as nociception. Concomitantly, the number of skin conductance fluctuations (NSCF) per second, measured using a Skin Conductance Algesimeter (SCA, MEDSTORM Innovation AS, Norway; > 0.27 fluctuations/sec indicating nociception), and the instantaneous Analgesia Nociception Index (iANI, MDoloris Medical Systems, France; < 50 indicating nociception) were collected. Tetanic stimulation resulted in a median pupillary dilation of 16 [6-25] % and a PPI of 5 [2-7]. According to the PPI assessment, 44 patients (55%) had nociception, whereas 23 (29%) and 18 (23%) showed nociception according to the algesimeter and iANI assessment, respectively. No significant changes in measured physiologic variables were observed after the tetanic stimulation. There were no correlations between PPI, post-stimulation iANI, and SCA-derived variables. There were no differences in PPI, iANI, and SCA variables in patients with low and normal baseline EEG power at baseline. PERSPECTIVES: Detection of nociception varies across different devices in unconscious critically ill patients. Further studies are required to understand which method to implement for analgesic administration in this patient population.

Diabetic neuropathic pain (DNP) is a common, complex, and severe complication of diabetes. It can lead to increased mortality, lower-limb amputations, and distressing neuropathic symptoms. Available therapies for DNP are broad-spectrum analgesics, related to various side effects. Transient receptor potential vanilloid-1 (TRPV1) is widely expressed within the peripheral and central nervous systems and plays an essential role in pain perception and regulation. Both TRPV1 agonists and antagonists could reduce the sensitivity to nociception. Some exhibit blood glucose homeostasis regulates function by influencing insulin secretion and receptor sensitivity. Since TRPV1 has exhibited the unique advantages of simultaneously managing blood sugar and pain, developing new TRPV1 channel modulators for diabetes-related pain syndrome is a promising alternative to conventional therapy. In this review, the role of TRPV1 in the pathogenesis of DNP has been described and challenges of TRPV1 modulators have been explored to be a new therapy for DNP.