Placebo Analgesia Flashcards
Define placebo effect
Placebo effects are beneficial effects that are attributable to the brain–mind responses to the context in which a treatment is delivered rather than to the specific actions of the drug - Wager & Atlas 2015
Define nocebo effects
Nocebo effects are detrimental effects that are attributable to the brain–mind responses to contexts of treatment administration rather than any specific effects of the treatment
4 types of external contexts of treatment examinations
- Verbal suggestions:“This is a highly effective painkiller that will make you feel better.”
- Place cues: Doctors office (could be placebo or nocebo depending on past experiences)
- Social cues: Eye gaze, body language, voice cues, white coat
- Treatment cues: Syringe, pills, needle puncture etc. Again, could be nocebo or placebo depending on the individual.
5 internal contexts of treatment administration
- Outcome expectancies: “My pain will go away”
- Emotions: Decreased anxiety
- Meaning schema:“I am being cared for”
- Explicit memories: Similar treatments that worked in the past
- Pre-cognitive associations (conditioning)
Define placebo analgesia
A reduction in pain that can be attributed to the treatment context.
What is ‘preconditioning’ in placebo analgesia?
Preconditioning is a classical conditioning mechanism where unconscious associations are formed between treatment contexts and pain relief.
The analgesic response is elicited by the same endogenous anti-nocioceptive network that was activated by the conditioned stimuli.
For example, if repeptitve pain relief was acheived using cannabinoids (e.g. CB1 agonists) then the placebo analgesia will be facilitated via the cannabinoid system. If conditioning occured with morphine, then it would be via the enkephelin system.
Other than pharmacological and placebo analgesia, how else may pain outcomes be affected? What can be done to control for this confound?
- Spontaneous fluctuation: Due to all types of stochastic factors and disease course, pain may fluctuate for reasons unassociated with either pharmacological intervention or placebo analgesia.
- Regression to the mean: People often seek medical assistance when the pain is maximal, therefore second assessments will tend to fall back to an average level
- False positives: When a co-intervention is the actual cause of the remission.
- Habituation or sensitisation: These are concerns in experimentally induced pain
The first two can be minimised in clincal experiments by taking a natural history (i.e., monitoring changes in the pain experienced over time when there is no intervention). False positives can be minimising by indepth interviews to identify and monitor any other interventions of the patient - particularly ‘holistic’ ones. Habituation and sensitisation can approached by minimising runs and maximising time between runs (Although time period cannot be too great or else they will not be relevant to one another because of changes of other confounding variables)
What are the two main pyschological mechanisms of placebo analgesia.
Expectation.
Conditioning.
What is the GABA disinhibition theory of descending modulation of pain?
That opioids and cannabinoids act to inhibit on tonically active GABAergic interneurons within the PAG and RVM to provide dishibition of projection neurons and analgesia
https://www.sciencedirect.com/science/article/pii/S0959438814001378
What are two common strategies against opioid hyperalgaesia?
- Opiate switching. Perhaps due to different affinities and efficacies, switching to different types of opiates can reduce OIH. (Different opiates have different agonist binding affinities and different instrinsic activity [response produced])
- NMDA block. Operating by similar mechanisms to LTP, NMDA block seems to relieve OIH. Ketamine.
What is the order mu receptor agonist affinity for common opiate analgesics?
Morphine
Fentanyl - fentayl produces much stronger response
Methadone
Codeine
Oxycodone
