lecture 10: placebo effects in analgesia

what is a placebo?

it is a psycho-socio-biological phenomenon that occurs when patients believe in an effective therapy they are receiving, thus experiencing a reduction of symptoms

what is a nocebo?

patients have a negative expectation which could trigger negative experiences; could be due to a pst experience and even a powerful analgesic can be hindered

what is the component of opium responsible for analgesia?

morphine

why do exogenous opioids work?

bc we have endogenous opioids called met-enkephalin + leu-enkephalin

what area of our CNS has loads of opioid receptors?

PAG

what components are involved in the placebo response?

a causal relationship b/w any medical procedure + psychosocial context surrounding the patient. this involves the RVM (w ON + OFF cells; on = pro-nociceptive) and a balance b/w facilitation & inhibitory descending modulation. another component involves the limbic system which can modulate the descending systems

why would the placebo effect be greater in experimental vs clinical trials?

clinical trials req you to tell patient there is a 50/50 chance of receiving the active drug vs placebo; experimental studies do not require this

what are placebo-related effects?

no placebo is given, and effects area attributed to influence of context surrounding treatment on patients brain (verbal suggestions can influence outcome)

which important mechs are involved in classical analgesia (2)?

1. opioid mechanism

2. cannabinoid mechanism

how can expectation vs classical-conditioning for clinical benefit impact opioid vs non-opioid (cannabinoid) systems?

expectation has a role in placebo-induced analgesia (expectation of reward → less pain → enhanced DA in N. acc → increased desc. pain inhibition via PAG)

• also can trigger endogenous opioids

conditioning can elicit a conditioned response similar to one induced by an opioid/non-opioid

• for opioid conditioning, placebo-analgesia is mediated via opioid receptors

• for non-opioid conditioning, thus utilises cannabinoid receptors

why are cannabinoid receptors important in non-opioid analgesia?

CB1-cannabinoid receptor antagonist (rimonabant) can BLOCK non-opioid analgesia, which demonstrates pharmacological conditioning can alter the recruitment of diff pain inhibitory systems during placebo analgesia

what problems come w identifying a REAL placebo effect?

• spontaneous remission

• false +ve errors

• regression to mean

• spontaneous variation in pain/illness

• clinical trial designs (telling patient of 50/50 chance0

what clinic trial designs are there ?

• double blind

  • randomised arm (1 = ppl given treatment, 2 = placebo)

• open vs hidden

  • open = see pump with something entering body

  • hidden = hidden pump, no idea when something enters body

what did the Colloca + Miller framework state?

integrated framework which posits that the placebo effect is a LEARNED response whereby several cues (verbal, condition, observational, social) can lead to a triggered expectation which generates behavioural + clinical outcome changes via CNS mechanisms