: Opioids are mu receptor agonists and have been an important part of pain treatment for thousands of years. In order to use these drugs appropriately and successfully in patients, whether to control pain, to treat opiate-induced side effects, or opiate withdrawal syndromes, a solid understanding of the pharmacology of such drugs is crucial. The most recognized full agonist opioids are heroin, morphine, codeine, oxycodone, meperidine, and fentanyl. Phenanthrenes refer to a naturally occurring plant-based compound that includes three or more fused rings. The opioids derived from the opium plant are phenanthrene derivatives, whereas most synthetic opioids are simpler molecules that do not have multiple rings. Methadone acts as a synthetic opioid analgesic similar to morphine in both quality and quantity; however, methadone lasts longer and in oral form, has higher efficacy, and is considered a diphenylheptane. Fentanyl is a strong synthetic phenylpiperdine derivative that exhibits activity as a mu-selective opioid agonist approximately 50 to 100 times more potent than morphine. Meperidine is another medication which is a phenylpiperdine. Tramadol is considered a mixed-mechanism opioid drug, as it is a centrally acting analgesic that exerts its effects via binding mu receptors and blocking the reuptake of monoamines. Some of the most common adverse effects shared among all opioids are nausea, vomiting, pruritus, addiction, respiratory depression, constipation, sphincter of Oddi spasm, and miosis (except in the case of meperidine). Chronic opioid usage has also established a relationship to opioid-induced hypogonadism and adrenal suppression. Physicians must be stewards of opioid use and use opioids only when necessary.

Context: Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs. Evidence Acquisition: An indexed MEDLINE search was conducted in July 2014, using keywords “analgesics”, “hepatic impairment”, “cirrhosis”, “acetaminophen or paracetamol”, “NSAIDs or nonsteroidal anti-inflammatory drugs”, “opioid” for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well. Results: Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance. Conclusions: No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting. Keywords: Adverse Drug Events; Hepatic Cirrhosis; Pain Management; Acetaminophen

Introduction: Osteoarthritis (OA) is a chronic joint disease that usually occurs in older people and leads to pain and disabilities. OA treatment ranges from drug therapy to surgery. Drug and rehabilitation therapy are preferred over surgery, and, especially, there is a tendency toward compounds causing regenerative changes in the knee joint. In the present study, the effects of platelet-rich plasma (PRP) injection and prolotherapy (PRL) were examined on the level of pain and function of the knee joint in patients with OA. Methodology: After fulfilling the inclusion criteria and signing the informed consent form, 42 patients with knee OA were scheduled for intra-articular injection in the present randomized, double-blind, clinical trial. Following admission to the operating pain room, the condition of the patient’s knee was evaluated first via the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and, then, ultrasound-guided knee injection was done. Accordingly, patients in the PRP therapy group received 7 mL PRP solution and those in the PRL group received 7 mL 25% dextrose. Using the WOMAC, levels of pain and knee function were evaluated and recorded for each patient immediately prior to the first injection as well as at 1 month (immediately prior to the second injection), 2 months (a month after the second injection), and 6 months later. Data collected were analyzed using the SPSS v.20. Results: During the first and second months, a rapid decrease in the overall WOMAC score was observed in both groups. The overall WOMAC score increased at the sixth month, but was lower than the overall WOMAC score in the first month. Statistical analysis indicated that the overall WOMAC score significantly decreased in both groups of patients over 6 months. Conclusion: Results of the present study suggested a significant decrease in the overall WOMAC score of patients who undergo either PRP therapy or PRL. This positive change in the overall WOMAC score led to an improvement in the quality of life of patients with knee OA shortly after the first injection. PRP injection is more effective than PRL in the treatment of knee OA.

Context: Chronic neuropathic pain is a common condition, and up to 11.9% of the population have been reported to suffer from uncontrolled neuropathic pain. Chronic pain leads to significant morbidity, lowered quality of life, and loss of workdays, and thus carries a significant price tag in healthcare costs and lost productivity. dorsal root ganglia (DRG) stimulation has been recently increasingly reported and shows promising results in the alleviation of chronic pain. This paper reviews the background of DRG stimulation, anatomical, and clinical consideration and reviews the clinical evidence to support its use. Evidence Acquisition: The DRG span the length of the spinal cord and house the neurons responsible for sensation from the periphery. They may become irritated by direct compression or local inflammation. Glial cells in the DRG respond to nerve injury, producing inflammatory markers and contribute to the development of chronic pain, even after the resolution of the original insult. While the underlying mechanism is still being explored, recent studies explored the efficacy of DRG stimulation and neuromodulation for chronic pain treatment. Results: Several reported cases and a small number of randomized trials were published in recent years, describing different methods of DRG stimulation and neuromodulation with promising results. Though evidence quality is mostly low, these results provide evidence to support the utilization of this technique. Conclusions: Chronic neuropathic pain is a common condition and carries significant morbidity and impact on the quality of life. Recent evidence supports the use of DRG neuromodulation as an effective technique to control chronic pain. Though studies are still emerging, the evidence appears to support this technique. Further studies, including large randomized trials evaluating DRG modulation versus other interventional and non-interventional techniques, are needed to further elucidate the efficacy of this method. These studies are also likely to inform the patient selection and the course of treatment.

Anesthesiology and Pain Medicine

Spinal block is a common procedure for lower limbs surgery. Fentanyl, a synthetic opioid and dexmedetomidine, a selective α2 agonist have been used as adjuvants in spinal anesthesia to prolong intraoperative and postoperative analgesia. The aim of current study is to compare the efficacy of dexmedetomidine and fentanyl added to intrathecal bupivacaine in orthopedic procedures in lower limbs. In this randomized clinical trial, 90 patients undergoing elective lower limb surgeries were randomly allocated to three groups. Via intrathecal approach, the patients received 2.5 ml hyperbaric bupivacaine 0.5% plus 5 micrograms dexmedetomidine (BD group), 25 micrograms fentanyl (BF group) or 0.5 ml normal saline (BN group), respectively. Time to reach the complete motor block, the highest sensory level, regression from block, analgesic request and duration of the drug effect, hemodynamic changes and side effects were compared between the groups. There was no significant difference between the groups regrading time to reach complete motor block, but time to reach the highest sensory level was shorter in group BD than group BF (6.28 ± 1.75 vs. 7.17 ± 1.45, p = 0.03). Group BD had significantly lower mean of NRS 6 h after operation (1.90 ± 0.84 vs. 6.16 ± 1.44 vs. 6.30 ± 1.17, p < 0.001) and longer duration to regress to Bromage 0 (331.60 ± 73.96 vs. 185.56 ± 35.87 vs. 147.03 ± 33.05 min, p < 0.001), to analgesic request (496.63 ± 70.19 vs. 296.33 ± 44.83 vs. 221.83 ± 22.26 min, p < 0.001), to regress two sensory levels (149.00 ± 23.17 vs. 88.90 ± 12.85 vs. 69.33 ± 6.67 min, p < 0.001) and to regress to S1 (560.53 ± 81.86 vs. 329.83 ± 44.10 vs. 241.83 ± 22.26 min, p < 0.001). Serial changes in SBP (p = 0.006), DBP (p = 0.03) and HR (p = 0.002) in group BF were significantly higher than the other two groups. The three groups had comparable side effects. Using dexmedetomidine as an adjuvant to bupivacaine for spinal anesthesia in lower limb surgeries has longer duration of sensory and motor block and longer postoperative analgesia. IRCT registration number: IRCT2017041010599N15 , 24 May 2017.