Endogenous opioids are naturally occuring peptides that act as both neurotransmitters and neuromodulators within the endogenous opioidergic system
There are multiple endogenous opioids, although the main ones are:
Endorphins
Enkephalins
Dynorphins
The primary function of relevance to anaesthetists is the involvement in modulating the reaction to painful stimuli
This involves both:
Setting the pain threshold (nociception)
Controlling nociceptive processing
Other functions
Modulation of gastrointestinal function
Regulation of vital functions including temperature homeostasis, hunger and thirst
Involvement in:
Mood and cognition
The immune response (neuro-immune axis)
Autonomic functions
Endocrine function
Endogenous opioids are derived from precursor proteins
The precursor proteins are found in high levels in the CNS, particularly in the hypothalamus/pituitary, peri-aqueductal gray (PAG), brainstem and the substantia gelatinosa of the spinal cord
Endorphins
The precursor pro-opioimelanocortin is cleaved into:
ACTH
β-lipotropin
β-lipotropin is a precursor to the endorphins:
β-endorphin
Ɣ-endorphin
β-endorophin is an agonist at all three classical opioid receptors
Enkephalins
Pro-enkephalin is a precursor protein which forms:
Leu-enkephalin
Met-enkephalin
They are agonists primarily at the delta (DOP) opioid receptor
Dynorphins
Pro-dynorphin is a precursor protein which forms:
Dynorphin A
Dynorphin B
They are agonists primarily at the kappa (KOP) opioid receptor
Others
Pre-pro-N/OFQ is cleaved into nociceptin/orphanin-FQ (N/OFQ), an endogenous opioid acting primarily at the N/OFQ (NOP) opioid receptor
The endomorphins (endomorphin 1 and 2) are endogenous opioids which act primarily at the mu (MOP) opioid receptor; their precursor protein is as-of-yet unidentified
Bradykinin
Serotonin
Histamine
Substance P
Calcitonin gene-related peptide (CGRP)
Endogenous cannabinoids (anandamide ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG))