title: Therapeutic Basis of Clinical Pain Modulation.
abstract: Pain is a hallmark of almost all bodily ailments and can be modulated by agents, including analgesics and anesthetics that suppress pain signals in the central nervous system. Defects in the modulatory systems, including the endogenous pain-inhibitory pathways, are a major factor in the initiation and chronicity of pain. Thus, pain modulation is particularly applicable to the practice of medicine. This review summarizes the existing literature on pain modulation. Here, we critically reviewed the literature from PubMed on pain modulation published primarily within the past 5 years in high impact journals. Specifically, we have discussed important anatomical landmarks of pain modulation and outlined the endogenous networks and underlying mechanisms of clinically relevant pain modulatory methods. The Gate Control Theory is briefly presented with discussion on the capacity of pain modulation to cause both hyper- and hypoalgesia. An emphasis has been given to highlight key areas in pain research that, because of unanswered questions or therapeutic potential, merit additional scientific scrutiny. The information presented in this paper would be helpful in developing novel therapies, metrics, and interventions for improved patient management.
authors.affiliation: Center for Clinical & Translational Science and Department of Anesthesiology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kirkpatrick
authors.affiliation: Center for Clinical & Translational Science and Department of Anesthesiology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Dan M
authors.initials: DM
authors.lastname: McEntire
authors.affiliation: Center for Clinical & Translational Science and Department of Anesthesiology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Zakary J
authors.initials: ZJ
authors.lastname: Hambsch
authors.affiliation: Center for Clinical & Translational Science and Department of Anesthesiology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Kerfeld
authors.affiliation: Center for Clinical & Translational Science and Department of Anesthesiology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Smith
authors.affiliation: Center for Clinical & Translational Science and Department of Anesthesiology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Reisbig
authors.affiliation: Center for Clinical & Translational Science and Department of Anesthesiology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Youngblood
authors.affiliation: Center for Clinical & Translational Science and Department of Anesthesiology, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D059331:Adrenergic Neurons / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism; D000700:Analgesics / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000777:Anesthetics / Q000627:therapeutic use; D000818:Animals; D001341:Autonomic Nervous System / Q000473:pathology; D002766:Cholecystokinin / Q000378:metabolism; D019004:Galanin / Q000378:metabolism; D006801:Humans; D006930:Hyperalgesia; D051379:Mice; D010146:Pain / Q000188:drug therapy; D059408:Pain Management / Q000379:methods*; D010919:Placebos; D051381:Rats; D043882:Receptors, Cannabinoid / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D000777:Anesthetics; D010919:Placebos; D043882:Receptors, Cannabinoid; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D019004:Galanin; D002766:Cholecystokinin
keywords: Gate Control Theory; cannabinoids; electroanalgesia; inhibitory amino acids; opioids; pain modulation; periaqueductal gray; rostral ventromedial medulla