Plants and Pain Flashcards
Plants used for halucinogenic modulating effects
- psilocibin - serotonin agonist
- ayahuasca - monoamine oxidase inhibitory (increase synaptic serotonin levels)
Plants used for Stimulant modulating effects
- coca leaves - dopamine reuptake inhibitor (increase synaptic dopamine levels)
- tobacco - cholinergic agonist nicotinic receptors
- coffee bean - adenosine receptor antagonist
Analgesic drugs derived from plants include
- salicylic acid (asprin)
- opiates (morphine, opium, thebaine)
- cannabis
- capsaicin
- menthol
- salvinorin
Primary Afferents
- sensory neurons in the periphery (skin, organs)
- two classes: A fibers and C fibers
Nociceptors
primary afferents that detect pain
A fibers are:
- myelinated (fast conducting, insulates the axon)
- end in specialized structures (Ruffini, Pacianian, Meissner)
- each structure detects specific non-painful stimuli (touch, temp, vibration)
C fibers are:
- unmyelinated (slow conducting)
- end as free nerve endings in the superficial layers of the skin
- detect many types of painful stimuli (thermal, mechanical, chemical, electrical)
- polymodal nociceptor
How are Painful Stimuli Detected?
- on the free nerve nerve endings of C fibres by specialized receptors
- TRPV1 : ion channel, activated by heat (> 43 degrees) and capsaicin, causes burning pain
- TRPA1 : allyl isothionate, burning, inflammation
Urishol
- found in poison ivy, crosses the skin and initates and inflammatory reaction that activates NK, BK and cytokine receptors
- causes itch and pain
How does info get sent up to the brain?
- C fibre primary afferents synapse onto secondary afferents in the dorsal horn of the spinal cord
- secondary afferents carry nociceptive information up the spinal cord to the brain
Nociception vs. Pain
- nociception does not equal pain
- nociception: relay of pain signal from periphery to the brain
- pain: integration of that pain signal with cognitive and emotional context (requires the brain, always a subjective experience)
Define opium, opiates, opioid
- opium : dried latex obtained from the poppy
- opiates : any drug derived from opium
- opioid: any drug that binds to an opioid receptor. Includes opiates, as well as synthetic opioid agonists (fentanyl, heroin, oxycontin)
Opioid Receptors in the body and their affect
- brain : many regions are involved in pain perception, emotion, reward and addiction
- brainstem : can affect breathing by quieting neurons that control respiration
- spinal cord
- peripheral neurons
- intestine
Agonists
- ex. morphine
- activate opioid receptors, but that activation leads to decreased likelihood that the neuron will fire
What are the 3 classes of opioid receptors?
mu, delta, kappa
receptor activation and typical agonists of mu opioid receptors
- receptor activation leads to analgesia euphoria
- typical agonists: heroin, morphine, oxycodone, fentanyl
receptor activation and typical agonists of delta opioid receptors
- receptor activation leads to decrease in anxiety
- typical agonists: some drugs being developed to treat chronic pain conditions, like migraine (SNC80)
receptor activation and typical agonists of kappa opioid receptors
- receptor activation leads to analgesia, dysphoria, hallucinations
- typical agonists: salvinorin
Dopamine
- dopamine is involved in motivated behavior
- dopamine neurons are located primarily in the VTA
- opioid recpetors in teh VTA are located on inhibitory GABAergic interneurons
- opioids inhibit inhibition (disinhibition) leading to dopamine release
How do opioid receptors inhibit pain?
- decreasing nociception at the level of the C fibre, in the spinal cord, and in the thalamus
- decreasing the emotional and cognitive aspects of pain (make the pain bother you less)
Define Cannabis and Cannabinoids
- cannabis: genus of flowering plant.Contains many bioactive compounds, but most studied are THC and CBD. THC is the primary psychoactive compound in cannabis
- cannabinoids: class of chemical compounds that act at the cannabinoid receptors
CB1 versus CB2 receptors
- CB1 receptors are among the most abundant GPCRs, found in brain, peripheral organs (heart, liver, fat, stomach, testes) and peripheral nerves
-CB2 receptor distribution mostly on immune cells
How Do Cannabinoids Work?
-cannabinoid receptors are inhibitory
G-protein coupled receptors (Gi
coupled)
- Cannabinoid receptors are located
on the presynaptic membrane
- cannabinoid receptors leads to decrease in cyclic adenosine
monophosphate (cAMP)
accumulation which inhibits the influx of calcium in the firing neuron and
inhibits neurotransmitter release.
- decrease synaptic transmission,
inhibit neurotransmitter release
THC Effects (general, potential therapeutic, and unwanted)
- is a partial agonist at CB1
- general : euphoria, relaxation, disinhibition, changes in perception, vasodilation, increase pulse rate
- potential therapeutic: attenuation of nausea, increased appetite, decreased intraocular pressure, chronic pain relief
- unwanted: memory impairment, dysphoric state, visual hallucinations, depersonalization, psychotic episodes, anxiety
CBD Effects
- some preclinical research suggests CBD has therapeutic potential for management of inflammation, anxiety, emesis, nausea, inflammatory pain, and epilepsy
- strong clinical data lacking for these claims
- pediatric epilepsy is the only condition in which high quality clinical data (oral CBD significantly reduced frequency of seizures more than placebo)
Adverse Effects of THC
- acute effects: panic attacks, severe anxiety, psychosis, paranoia, convulsions, hyperemesis
- prenatal effects: neuroanatomical and behavioral changes in offspring (dose-response relationship not identified)
- lung cancer: smoked cannabis
- driving: increase risk of accident
- no documented evidence of death - sparsity of CB1 receptors in the brain stem region that controls respiratory and cardiovascular systems
Define Psychological Dependence
compulsive drug-seeking behavior in which the individual uses the drug receptively for personal satisfaction, often in the face of known risks to health
Define Physiological Dependence
revealed when withdrawal of the drug produces symptoms and signs that are frequently opposite of those sought by the user
Cannabis Withdrawal
- is relatively mild and short-lived
- symptoms of restlessness, irritability, mild agitation, insomnia, nausea and cramping
- may be worse in chronic, long-term users and may contribute to continues drug use
Define Addiction (Substance use disorder)
inability to control the use of legal or illegal substances despite negative consequences
The Challenge of Cannabinoid Pharmacology
- smoked cannabis may be effective at treating conditions like chronic pain, chemotherapy induced nausea and others
- smoked plant not ideal because hard to control dose
- efforts to design synthetic cannabinoids (CB1 or CB2 agonists) - some success, but not nearly as effective as smoked cannabis
