What do plasma beta-endorphin levels reveal about endogenous opioid analgesic function? – Sept 2003 – free full-text PMC article
Plasma levels of beta-endorphin (BE), an endogenous opioid analgesic, are often reported as they relate to acute and chronic pain outcomes.
However, little is known about what resting plasma BE levels might reveal about functioning of the endogenous opioid antinociceptive system.
This study directly examined associations between resting plasma BE and subsequent endogenous opioid analgesic responses to acute pain in 39 healthy controls and 37 individuals with chronic low back pain (LBP).
Resting baseline levels of plasma BE were assessed. Next, participants received opioid blockade (8 mg naloxone i.v.) or placebo in a double-blind, randomized, crossover design. Participants then underwent two acute pain stimuli: finger pressure (FP) pain and ischaemic (ISC) forearm pain. Blockade effects (naloxone minus placebo pain ratings) were derived to index endogenous opioid analgesic function.
In placebo condition analyses for both pain stimuli, higher resting BE levels were associated with subsequently greater reported pain intensity (p’s < 0.05), with this effect occurring primarily in healthy controls (BE × Participant Type interactions, p’s < 0.05).
In blockade effect analyses across both pain tasks, higher resting plasma BE predicted less subsequent endogenous opioid analgesia (smaller blockade effects; p’s < 0.05).
For the ISC task, these links were significantly more prominent in LBP participants (BE × Participant Type Interactions, p’s < 0.05).
Results suggest that elevated resting plasma BE may be a potential biomarker for reduced endogenous opioid analgesic capacity, particularly among individuals with chronic pain. Potential clinical implications are discussed
The primary aim of this study was to directly evaluate associations between resting plasma BE (beta-endorphin) and opioid blockade-derived indices of opioid antinociceptive function in a relatively large sample, including chronic pain patients.
Placebo condition results indicated that for all significant associations across both pain tasks, higher resting plasma BE levels were associated with greater subsequent pain responsiveness.
this positive resting BE/pain intensity link was restricted primarily to the healthy participant group.
associations between higher resting BE and greater placebo pain intensity might be related to lower endogenous opioid analgesia during acute pain stimulation
These latter findings suggest that elevated resting plasma BE levels may be particularly relevant as a biomarker for reduced endogenous opioid antinociceptive function in chronic pain patients.
On the face of it, an association between higher circulating BE and lower subsequent endogenous opioid analgesia appears counter-intuitive. However, to the extent that resting plasma BE levels might also reflect tonic activation of CNS opioid pathways, the results of this study could be due to the influence of opioid receptor down-regulation
Release of BE from the pituitary into circulation is part of the systemic stress response and elevated emotional arousal is often associated with HPA activation
Elevated BE in the current study could have been a reflection of greater tonic activation of stress systems, which might have reduced central opioid analgesic function via receptor down-regulation as previously described.
In summary, the current findings indicate that elevated resting plasma BE levels are associated with lower endogenous opioid analgesia. These findings were consistent across two different experimental acute pain stimuli and both primary and secondary pain outcomes.
Whether individuals with chronic pain have impaired or upregulated endogenous opioid systems, interventions that increase endogenous opioid activity may in either case have clinical applications.
Findings of the current study also suggest the potential clinical utility of assessing plasma BE values.
For example, if large normative datasets were available as a reference, higher resting plasma BE values might identify individuals most likely to have exaggerated pain responses and inadequate endogenous antinociceptive activity.
These individuals might consequently require more aggressive pain management in the post-surgical or other clinical contexts. The fact that inverse associations between resting BE and opioid analgesic function in this study were particularly prominent in individuals with chronic pain suggests possible clinical utility of this measure in the context of chronic pain management as well.