Pain and addiction

Psychedelics are hallucinogenic drugs that alter the state of consciousness substantially. They bring about psychological, auditory, and visual changes. The psychedelics act on the brain, implying that they have a powerful psychological impact. One of the main factors contributing to disability worldwide is pain. The majority of people deal with pain on a daily basis. Living with chronic pain affects daily life and has social implications. Chronic pain can be associated with any disease that may be genetic, idiopathic, or traumatic...

The research of new therapeutic strategies for neuropathic pain represents a major current priority. Important drawbacks to advance in the development of these therapies are the limited translational value of the animal models now available and the elucidation of the complex neuronal and immune pathophysiological mechanisms underlying neuropathic pain. One of the neurotransmitter systems participating in neuropathic pain control that has recently raised a particular interest is the endocannabinoid system. This system is highly expressed in neurons and immune cells, and it plays a crucial role in the development of neuropathic pain...

Human genetic studies have implicated the voltage-gated sodium channel NaV 1.7 as a therapeutic target for the treatment of pain. A novel peptide, μ-theraphotoxin-Pn3a, isolated from venom of the tarantula Pamphobeteus nigricolor, potently inhibits NaV 1.7 (IC50 0.9 nM) with at least 40-1000-fold selectivity over all other NaV subtypes. Despite on-target activity in small-diameter dorsal root ganglia, spinal slices, and in a mouse model of pain induced by NaV 1.7 activation, Pn3a alone displayed no analgesic activity in formalin-, carrageenan- or FCA-induced pain in rodents when administered systemically...

Morphine is widely used for clinical pain management and induces the dependence. Addiction to morphine is a major public health issue. Geranylgeranylacetone (GGA) is widely used in clinic for treating ulcer. GGA induces expression of thioredoxin-1 (Trx-1) extensively. Trx-1 is a redox regulating protein and plays protecting roles in nervous system. GGA prevents mice against morphine-induced hyperlocomotion, rewarding effect, and withdrawal syndrome. However, whether GGA blocks morphine-conditioned place preference (CPP) reinstatement is still unknown...

OBJECTIVE: To characterize the functional brain changes involved in δ-9-tetrahydrocannabinol (THC) modulation of chronic neuropathic pain. METHODS: Fifteen patients with chronic radicular neuropathic pain participated in a randomized, double-blind, placebo-controlled trial employing a counterbalanced, within-subjects design. Pain assessments and functional resting state brain scans were performed at baseline and after sublingual THC administration. We examined functional connectivity of the anterior cingulate cortex (ACC) and pain-related network dynamics using graph theory measures...

There is significant overlap in the pharmacological management of pain and psychological disorders. Appropriate treatment of patients' comorbid psychological disorders, including sleep disturbances often leads to an improvement in reported pain intensity. The three first line agents for neuropathic pain include tricyclic antidepressants and serotonin norepinephrine reuptake inhibitors which are medications originally developed as antidepressants. The other first line medication for chronic neuropathic pain are anticonvulsant medications initially brought to the market-place for the treatment of epilepsy and are also now being used for the treatment of anxiety disorders and substance withdrawal symptoms...

The buprenorphine receptor binding profile is unique in that it binds to all three major opioid receptors (mu, kappa, delta), and also binds to the orphan-like receptor, the receptor for orphanin FQ/nociceptin, with lower affinity. Within the mu receptor group, buprenorphine analgesia in rodents is dependent on the recently discovered arylepoxamide receptor target in brain, which involves a truncated 6-transmembrane mu receptor gene protein, distinguishing itself from morphine and most other mu opioids. Although originally designed as an analgesic, buprenorphine has mainly been used for opioid maintenance therapy and only now is increasingly recognized as an effective analgesic with an improved therapeutic index relative to certain potent opioids...

BACKGROUND: Acute pain is a common condition among prehospital patients and prompt management is pivotal. Opioids are the most frequently analgesics used in the prehospital setting. However, opioids are highly addictive, and some patients may develop opioid dependence, even when they are exposed to brief opioid treatments. Therefore, alternative non-opioid analgesia should be developed to manage pain in the prehospital setting. Used at subdissociative doses, ketamine, a noncompetitive N-methyl-D-aspartate and glutamate receptor antagonist, provides analgesic effects accompanied by preservation of protective airway reflexes...

Neuropathic pain has a substantial effect on quality of life (QOL). The Japanese Society of Pain Clinicians (JSPC) has developed clinical guidelines of pharmacotherapy for neuropathic pain. These guidelines offer clarity on recommendations based on both the most recent scientific evidence and expert opinions. Understanding the concept, disease entity, and burden of neuropathic pain, as well as its screening and diagnosis are important steps before starting pharmacotherapy. As well as other guidelines, the guidelines propose several lines of pharmacotherapies in a step-wise manner...

OBJECTIVE: The authors sought to determine whether cannabis use is associated with a change in the risk of incident nonmedical prescription opioid use and opioid use disorder at 3-year follow-up. METHOD: The authors used logistic regression models to assess prospective associations between cannabis use at wave 1 (2001-2002) and nonmedical prescription opioid use and prescription opioid use disorder at wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions...

We have reviewed here the neuroanatomical and neuropsychological literature of the human brain and have proposed the various pain mechanisms that we currently know of. Essentially when tissue is damaged, peripheral nociceptors are activated continuously and prostanoids are hence produced. Nonsteroidal anti-inflammatory drugs (NSAIDs) and medications aim to target these prostanoids to treat the inflammatory component of pain. Normal pain tends to have a protective response. It is important for the nervous system to learn and recognize this painful stimulus earlier and quicker with repeated exposure to avoid tissue damage...

The use of the opioid antagonist naloxone is well known to the experienced health care provider. The availability of the longer acting opioid antagonist nalmefene has several potential benefits in clinical practice. Nalmefene has a plasma half-life of almost 11 h, compared to 60-90 min for naloxone. Nalmefene has been shown to reverse opioid intoxication for as long as 8 h, reducing the need for continuous monitoring of intoxicated patients and repeated dosing of naloxone. Single dose administration has also been used effectively in the reversal of opiate-assisted conscious sedation...

STUDY OBJECTIVE: We assess and compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine with morphine in emergency department (ED) patients. METHODS: This was a prospective, randomized, double-blind trial evaluating ED patients aged 18 to 55 years and experiencing moderate to severe acute abdominal, flank, or musculoskeletal pain, defined as a numeric rating scale score greater than or equal to 5. Patients were randomized to receive ketamine at 0...

BACKGROUND: Sublingual buprenorphine-naloxone (buprenorphine SL) is a preparation that is used to treat opioid dependence. In addition, the Drug Enforcement Administration (DEA) has acknowledged the legality of an off-label use to treat pain with a sublingual buprenorphine preparation. Buprenorphine SL is unique among the opioid class of analgesics; this compound has a high affinity for the mu-receptor, yet only partially activates it. Thus, buprenorphine SL can provide analgesia, yet minimize opioid side effects...