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AAG: α1-acid glycoprotein

AC: adenylyl cyclase

ACE: angiotensin-converting enzyme

ACh: acetylcholine

ACTH: corticotropin; formerly adrenocorticotropic hormone

ADH: antidiuretic hormone

ADME: absorption, distribution, metabolism, excretion

AT1: angiotensin II receptor, type 1

ATC: around the clock

BBB: blood-brain barrier

CaMK: Ca2+/calmodulin-dependent protein kinase

CDC: Centers for Disease Control and Prevention

CLIP: corticotropin-like intermediate lobe peptide

CNS: central nervous system

COPD: chronic obstructive pulmonary disease

COX: cyclooxygenase

CRH: corticotropin-releasing hormone

CSF: cerebrospinal fluid

CYP: cytochrome P450

DA: dopamine

DAMGO: [D-Ala2,MePhe4,Gly(ol)5]enkephalin

DHEA: dehydroepiandrosterone

DOR: δ opioid receptor

DYN: dynorphin

EEG: electroencephalogram

β-END: β-endorphin

L-ENK: Leu-enkephalin

ER/LA: extended-release/long-acting (a)

FDA: Food and Drug Administration

FSH: follicle-stimulating hormone

GABA: γ-aminobutyric acid

GI: gastrointestinal

GIRK: G protein–activated inwardly rectifying K+ channel

GnRH: gonadotropin-releasing hormone

GPCR: G protein-coupled receptor

GRK: GPCR kinase

HPA: hypothalamic-pituitary-adrenal

5HT: serotonin

IM: intramuscular

IP3: inositol triphosphate

IV: intravenous

JNK: c-Jun N-terminal kinase

KOR: κ opioid receptor

LH: luteinizing hormone

LPH: lipotropin

6-MAM: 6-monoacetylmorphine

MAO: monoamine oxidase

MAP: mitogen-activated protein

M-ENK: Met-enkephalin

MME: morphine milligram equivalent

MOR: μ opioid receptor

MSH: melanocyte-stimulating hormone

NAc: nucleus accumbens

NE: norepinephrine

α-NEO: α neoendorphin

NF-κB: nuclear factor kappa B

NMDA: N-methyl-D-aspartate

NOP: nociceptin/orphanin FQ (N/OFQ) receptor

NSAID: nonsteroidal anti-inflammatory drug

PAG: periaqueductal gray

PCA: patient-controlled anesthesia

PDMP: prescription drug monitoring program

PFC: prefrontal cortex

PI3K: phosphoinositide 3 kinase

PK: protein kinase

PLC: phospholipase C

POMC: pro-opiomelanocortin

pre-proDYN: pre-prodynorphin

pre-ProENK: pre-proenkephalin

SNRI: serotonin-norepinephrine reuptake inhibitor

SSRI: selective serotonin reuptake inhibitor

TM: transmembrane

VP: ventral pallidum

VTA: ventral tegmental area


Pain is a component of virtually all clinical pathologies, and management of pain is a primary clinical imperative. Opioids are a mainstay of acute pain treatment, but in recent years, the efficacy and safety of long-term use of opioids to treat chronic pain has been questioned as instances of addiction and death from their misuse have mounted. Opioids are certainly no longer first-line treatment of chronic pain, and a more conservative approach may involve other drug classes, such as NSAIDs, anticonvulsants, and antidepressants.

The term opiate refers to compounds structurally related to products found in opium, a word derived from opos, the Greek word for “juice,” natural opiates being derived from the resin of the opium poppy, Papaver somniferum. Opiates include the natural plant alkaloids, such as morphine, codeine, thebaine, and many semisynthetic derivatives. An opioid is any agent that has the functional and pharmacological properties of an opiate. Endogenous opioids are naturally occurring ligands for opioid receptors found in animals. The term endorphin not only is used synonymously with endogenous opioid peptides but also refers to a specific endogenous opioid, β-endorphin. The term narcotic was derived from the Greek word narkotikos, for “benumbing” or “stupor.” Although the term narcotic originally referred to any drug that induced narcosis or sleep, ...

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