Descending facilitation from rostral ventromedial medulla mu opioid receptor-expressing neurons is necessary for maintenance of sensory and affective dimensions of chronic neuropathic pain.

ABSTRACT: Pharmacological ablation of rostral ventromedial medulla (RVM) mu opioid receptor-expressing cells before peripheral nerve injury prevents the development of neuropathic pain. However, whether these neurons are required for the expression of established neuropathic pain is not known. Male Oprm1Cre heterozygous (MORCre) or wild-type (MORWT) mice received AAV8-hSyn-DIO-hM4D(Gi)-mCherry in the RVM. After partial sciatic nerve ligation (PSNL), we evaluated pain behaviors and descending control of nociception in response to acute or sustained chemogenetic inhibition of RVM-MOR cells expressing hM4D(Gi). A single systemic administration of hM4D(Gi) agonist clozapine-N-oxide (CNO) reversibly inhibited hind paw tactile allodynia and produced conditioned place preference only in MORCre mice with PSNL. Intrathecal CNO also reversibly inhibited PSNL-induced hind paw allodynia, suggesting that the spinal projections from these RVM-MOR cells are critical for manifestation of pain behaviors. Consistent with enhanced descending facilitation from RVM-MOR cells, MORCre-hM4D(Gi) mice with PSNL showed diminished descending control of nociception that was restored by systemic CNO. Sustained CNO in drinking water before PSNL prevented expression of chronic pain without affecting acute surgical pain; however, relief of chronic pain required sustained CNO treatment. Thus, in male mice, activity of spinally projecting RVM-MOR cells is required (1) for expression and manifestation of both sensory and affective dimensions of established neuropathic pain and (2) to promote descending facilitation that overcomes apparently intact descending inhibition to maintain chronic pain. Enhanced descending facilitation likely regulates the output signal from the spinal cord to the brain to shape the pain experience and may provide a mechanism for nonopioid management of pain.

Medical Cannabis for Chronic Nonmalignant Pain Management.

PURPOSE OF REVIEW: Cannabis has been used since ancient times for medical and recreational research. This review article will document the validity of how medical cannabis can be utilized for chronic nonmalignant pain management. RECENT FINDINGS: Current cannabis research has shown that medical cannabis is indicated for symptom management for many conditions not limited to cancer, chronic pain, headaches, migraines, and psychological disorders (anxiety and post-traumatic stress disorder). Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are active ingredients in cannabis that modulate a patient's symptoms. These compounds work to decrease nociception and symptom frequency via the endocannabinoid system. Research regarding pain management is limited within the USA as the Drug Enforcement Agency (DEA) classifies it as a schedule one drug. Few studies have found a limited relationship between chronic pain and medical cannabis use. A total of 77 articles were selected after a thorough screening process using PubMed and Google Scholar. This paper demonstrates that medical cannabis use provides adequate pain management. Patients suffering from chronic nonmalignant pain may benefit from medical cannabis due to its convenience and efficacy.

Blunt trauma related chest wall and pulmonary injuries: An overview.

Physical traumas are tragic and multifaceted injuries that suddenly threaten life. Although it is the third most common cause of death in all age groups, one out of four trauma patients die due to thoracic injury or its complications. Blunt injuries constitute the majority of chest trauma. This indicates the importance of chest trauma among all traumas. Blunt chest trauma is usually caused by motor vehicle accident, falling from height, blunt instrument injury and physical assault. As a result of chest trauma, many injuries may occur, such as pulmonary injuries, and these require urgent intervention. Chest wall and pulmonary injuries range from rib fractures to flail chest, pneumothorax to hemothorax and pulmonary contusion to tracheobronchial injuries. Following these injuries, patients may present with a simple dyspnea or even respiratory arrest. For such patient, it is important to understand the treatment logic and to take a multidisciplinary approach to treat the pulmonary and chest wall injuries. This is because only 10% of thoracic trauma patients require surgical operation and the remaining 90% can be treated with simple methods such as appropriate airway, oxygen support, maneuvers, volume support and tube thoracostomy. Adequate pain control in chest trauma is sometimes the most basic and best treatment. With definite diagnosis, the morbidity and mortality can be significantly reduced by simple treatment methods.