The reason opioid medications work so well is that they mimic the structure and function of the opioids naturally produced by our own bodies.
This is also why I’m more comfortable with these medications than many of the other strange molecules designed to ease pain, like antiepileptics and antidepressants.
First, some basic definitions from Wikipedia:
Endorphins – Wikipedia
The term implies a pharmacological activity (analogous to the activity of the corticosteroid category of biochemicals) as opposed to a specific chemical formulation. It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean “a morphine-like substance originating from within the body”.
Opioid peptides – Wikipedia
Such peptides may be produced by the body itself, for example endorphins.
The effects of these peptides vary, but they all resemble those of opiates.
Brain opioid peptide systems are known to play an important role in
Below are 5 PubMed articles related to the function and dysfunction of our endogenous opioids.
Dysfunctional Endogenous Opioid System
Exercise is an effective treatment for various chronic pain disorders, including
- chronic neck pain,
- rheumatoid arthritis, and
- chronic low back pain.
Although the clinical benefits of exercise therapy in these populations are well established (i.e. evidence based), it is currently unclear whether exercise has positive effects on the processes involved in chronic pain (e.g. central pain modulation).
Reviewing the available evidence addressing the effects of exercise on central pain modulation in patients with chronic pain.
Exercise activates endogenous analgesia in healthy individuals.
The increased pain threshold following exercise is due to the release of endogenous opioids and activation of (supra)spinal nociceptive inhibitory mechanisms orchestrated by the brain.
Exercise triggers the release of beta-endorphins from the pituitary (peripherally) and the hypothalamus (centrally), which in turn enables analgesic effects by activating μ-opioid receptors peripherally and centrally, respectively.
The hypothalamus, through its projections on the periaqueductal grey, has the capacity to activate descending nociceptive inhibitory mechanisms.
However, several groups have shown dysfunctioning of endogenous analgesia in response to exercise in patients with chronic pain.
Muscle contractions activate generalized endogenous analgesia in healthy, pain-free humans and patients with either osteoarthritis or rheumatoid arthritis, but result in increased generalised pain sensitivity in fibromyalgia patients.
In patients having local muscular pain (e.g. shoulder myalgia), exercising non-painful muscles activates generalized endogenous analgesia.
However, exercising painful muscles does not change pain sensitivity either in the exercising muscle or at distant locations.
The reviewed studies examined acute effects of exercise rather than long-term effects of exercise therapy.
A dysfunctional response of patients with chronic pain and aberrations in central pain modulation to exercise has been shown, indicating that exercise therapy should be individually tailored with emphasis on prevention of symptom flares.
The paper discusses the translation of these findings to rehabilitation practice together with future research avenue.
Endogenous Opioids and Anger
Evidence suggests that anger and pain are related, yet it is not clear by what mechanisms anger may influence pain. We have proposed that effects of anger states and traits on pain sensitivity are partly opioid mediated.
In this study, we test the extent to which analgesic effects of acute anger arousal on subsequent pain sensitivity are opioid mediated by subjecting healthy participants to anger-induction and pain either under opioid blockade (oral naltrexone) or placebo.
Participants were 160 healthy individuals. A double-blind, placebo-controlled, between-subjects opioid blockade design is used, with participants assigned randomly to one of two drug conditions (placebo or naltrexone), and to one of two Task Orders (anger-induction followed by pain or vice versa).
Results of ANOVAs show significant Drug Condition x Task Order interactions for sensory pain ratings (MPQ-Sensory) and angry and nervous affect during pain-induction, such that
participants who underwent anger-induction prior to pain while under opioid blockade (naltrexone) reported more pain, and anger and nervousness than those who underwent the tasks in the same order, but did so on placebo.
Results suggest that for people with intact opioid systems, acute anger arousal may trigger endogenous opioid release that reduces subsequent responsiveness to pain. Conversely, impaired endogenous opioid function, such as that found among some chronic pain patients, may leave certain people without optimal buffering from the otherwise hyperalgesic affects of anger arousal, and so may lead to greater pain and suffering following upsetting or angry events.
The anger management styles of anger-in (inhibition) and anger-out (direct expression) are positively associated with pain responsiveness.
Opioid blockade studies suggest that hyperalgesic effects of trait anger-out, but not those of trait anger-in, are mediated in part by opioid analgesic system dysfunction.
The current study tested the opioid dysfunction hypothesis of anger-out using an alternative index of opioid function: pain-induced changes in plasma endogenous opioids.
Plasma beta-endorphin (BE) was assessed at rest and again following exposure to three laboratory acute pain tasks (finger pressure, ischemic, and thermal) in 14 healthy controls and 13 chronic low back pain (LBP) subjects.
As expected, acute pain ratings correlated positively with measures of anger-in (both groups) and anger-out (LBP group; p’s<.05).
Greater pain-induced increases in BE were associated with significantly lower pain ratings in both groups (p’s<.05).
Hierarchical multiple regression indicated that greater anger-out significantly predicted smaller pain-induced beta-endorphin increases (p<.05).
Subject type did not moderate this association (p>.10).
Anger-in did not display significant main or interaction effects on pain-induced beta-endorphin changes (p’s>.10).
The significant association between anger-out and beta-endorphin release partially mediated the hyperalgesic effects of anger-out on pain unpleasantness, and was not attenuated by statistical control of general negative affect.
This suggests unique associations with expressive anger regulation.
Elevated trait anger-out therefore appears to be associated with opioid analgesic system dysfunction, whether it is indexed by responses to opioid blockade or by examining circulating endogenous opioid levels.
Possible “state x trait” interactions on these anger-related opioid system differences are discussed.
Disruptions of the Endogenous Opioid System
(for better or worse)
Nicotine effects and the endogenous opioid system. – PubMed – NCBI – J Pharmacol Sci. 2014
Nicotine (NIC) is an exogenous ligand of the nicotinic acetylcholine receptor (nAChR), and it influences various functions in the central nervous system.
Systemic administration of NIC elicits the release of endogenous opioids (endorphins, enkephalins, and dynorphins) in the supraspinal cord. Additionally, systemic NIC administration induces the release of methionine-enkephalin in the spinal dorsal horn.
NIC has acute neurophysiological actions, including antinociceptive effects, and the ability to activate the hypothalamic-pituitary-adrenal (HPA) axis.
If nicotine has antinociceptive effects, why do I see so many articles insisting that smoking increases pain? I suspect such articles may be nothing more than scare stories trying to further demonize cigarettes.
The endogenous opioid system participates in NIC-induced antinociception, but not HPA axis activation.
Moreover, NIC-induced antinociception is mediated by α4β2 and α7 nAChRs, while NIC-induced HPA axis activation is mediated by α4β2, not α7, suggesting that the effects of NIC on the endogenous opioid system are mediated by α7, not α4β2. NIC has substantial physical dependence liability.
The opioid-receptor antagonist naloxone (NLX) elicits NIC withdrawal after repeated NIC administration, and NLX-induced NIC withdrawal is inhibited by concomitant administration of an opioid-receptor antagonist.
NLX-induced NIC withdrawal is also inhibited by concomitant administration of an α7 antagonist, but not an α4β2 antagonist. Taken together, these findings suggest that NIC-induced antinociception and the development of physical dependence are mediated by the endogenous opioid system, via the α7 nAChR.
The mu and delta types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors.
we showed that chronic, but not acute, morphine treatment caused an increase in the abundance of mu-delta heteromers in key areas of the central nervous system that are implicated in pain processing.
Because of its distinct signaling properties, the mu-delta heteromer could be a therapeutic target in the treatment of chronic pain and addiction.