Pathophysiology of Chronic Pain
Keywords:
epigenetics, memory, central sensitization, chronic painAbstract
Acute pain hurts and most often is the result of tissue injury. Chronic pain also hurts. Although those who suffer from chronic pain also tend to associate the onset with an injury, illness, or surgical procedure; the root cause is far more complex. Chronic pain most often does not follow dermatomal distributions associated with any injury, disease or surgical procedure. And more often than not, chronic pain sufferers also suffer from various forms of depression and/or anxiety. The process of central sensitization resulting from tissue injury has been elucidated, as has many of the molecular changes within the brain that perpetuate chronic pain. Genetics, epigenetics, environmental stressors, and emotional stressors all play roles to varying degrees in the development of the chronic pain state. This article explores how synaptic memories form in the brain as a result of both physical and emotional traumas (multiple hits) resulting in progression to chronic pain, because of failure of the brain’s descending modulatory mechanisms to prevent or control “the pain”.
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https://en.wikipedia.org/wiki/Antigonish_(poem)
Ochoa JL. Guest Editorial: Essence, investigation, and management of “neuropathic” pains: Hopes from acknowledgement of chaos. Nerve & Muscle 1993; 16: 997–1008
Schofferman J, Anderson D, Hines R, Smith G, White A. Childhood psychological trauma correlates with unsuccessful lumbar spine surgery. Spine 1992; 17(6 Suppl):S138–44
Borsook D, Edwards R, Elman I, Becerra L, Levine J. Pain and analgesia: The value of salience circuits. Progress in Neurobiology 2013; 104 93–105
Turk DC, Vierck CJ, Scarbrough E, Crofford LJ, and Rudin NJ. Fibromyalgia: Combining pharmacological and nonpharmacological approaches to treating the person, not just the pain. The Journal of Pain 2008; 9, No 2: 99–104
Vierck Jr. CJ. Mechanisms underlying development of spatially distributed chronic pain (fibromyalgia) Pain 2006; 124 : 242–263
Bonica JJ, Loeser JD, Chapter 1: History of pain concepts and therapies. In: Bonica’s Management of Pain, third edition: Loeser JD et al editors, Lippincott Williams & Wilkins, Philadelphia, 2001
Perkins FM and Kehlet H. Chronic pain as an outcome of surgery: A review of predictive factors. Anesthesiology 2000; 93:1123–33
Deumens R, Steyaert A, Forget P, Schubert M, Lavand’homme P, et al. Prevention of chronic postoperative pain: Cellular, molecular, and clinical insights for mechanism-based treatment approaches. Progress in Neurobiology 2013; 104: 1–37
Chan C-W and Peng P. Failed back surgery syndrome. Pain Medicine 2011;12: 577–606
Nikolajsen L, Brandsborg B, Lucht U, Jensen TS and Kehlet H. Chronic pain following total hip arthroplasty: a nationwide questionnaire study. Acta Anesthesiol Scand 2006; 50: 495–500
Brander VA, Stulberg, SD, Adams AD, Harden RN, et al. Ranawat Award Paper: Predicting total knee replacement pain: A prospective, observational study. Clinical Orthopaedics & Related Research 2003; 416:27–36
Merskey H, Albe-Fessard DG, Bonica JJ, et al. Pain terms: a list with definitions and notes on usage: recommended by the IASP Subcommittee on Taxonomy. Pain 1979; 6: 249–52
CLASSIFICATION OF CHRONIC PAIN: DESCRIPTIONS OF CHRONIC PAIN SYNDROMES AND DEFINITIONS OF PAIN TERMS; Second Edition. Prepared by the Task Force on Taxonomy of the International Association for the Study of Pain (IASP) Editors Merskey H, Bogduk N, 1994 (Reprinted 2002), IASP PRESS • SEATTLE
Jacobs MS. The Mind and Body in Pain: Psychoanalytic Work and the Phenomenology of Suffering: The Phenomenology of suffering: Treating the mind and body in pain. Committee on Psychoanalysis and Health Care Invited Symposium: Division of Psychoanalysis of the American Psychological Association Spring Meeting 2015 – San Francisco
Dickinson BD, Hend CA, Gitlow S, Osbahr AJ. Maldynea: Pathophysiology and management of neuropathic and maladaptive pain-A report of the AMA council on science and public health. Pain Medicine 2010; 11:1635–53
Siddell PJ, Cousins MJ. Persistent pain as a disease entity: Implications for clinical management. Anesth Analg. 2004; 99 (2):510–20
Cousins MJ. Pain: The past, present, and future of Anesthesiology? The E. A. Rovenstine Memorial Lecture. Anesthesiology 1999; 91.558–51
Chapman CR, Psychophysiology of pain: Chapter 24 In: Bonica’s Management of Pain 3rd edition, Loeser J chief editor, Lippincott, Philadelphia, 2001
Fitzgibbon D and Chapman CR. Cancer pain: Assessment and diagnosis, Chapter 35. In: Bonica’s Management of Pain 3rd edition, Loeser J chief editor, Lippincott, Philadelphia, 2001
Chapmanert CR, Tuckett RP, and Song CW. Pain and stress in a systems perspective: Reciprocal neural, endocrine, and immune interactions. The Journal of Pain 2008; 9 No 2:122–145
Blackburn-Munro G, Blackburn-Munro R. Pain in the brain: Are hormones to blame? Trends Endocrinol Metab 2003; 14:20–7
Robinson S. J., Sunram-Lea S. I., Leach J., and Owen-Lynch P. J. The effects of exposure to an acute naturalistic stressor on working memory, state anxiety and salivary cortisol concentrations. Stress (Amsterdam, Netherlands) 2008; 11(2): 115–124
Buchheit T, Van de Ven T, and Shaw A. Epigenetics and the transition from acute to chronic pain. Pain Medicine 2012; 13: 1474–1490
Steinman L. Elaborate interactions between the immune and nervous systems. Nat Immunol. 2004; 5(6):575–81
Straub RH, Del Rey A, Besedovsk HO. Chapter 10 – Emerging concepts for the pathogenesis of chronic disabling inflammatory diseases: Neuroendocrine-immune interactions and evolutionary biology. In: Psychoneuroimmunology (Fourth Edition), Ader R. editor. Elsevier, Boston. 2007
Melzak R, Torgerson WS. On the language of pain. Anesthesiology 1971; 34 No 1:50–59
Engel GL. “Psychogenic” pain and the pain prone patient. Am J of Med 1959; 26:899–918
Duncko R., Johnson L., Merikangas K., and Grillon C. Working memory performance after acute exposure to the cold pressor stress in healthy volunteers. Neurobiology of Learning and Memory 2009; 91(4), 377–381
Funahashi S. Neuronal mechanisms of executive control by the prefrontal cortex. Neurosci Res. 2001; 39:147 – 165
Jänig W, McLachlan EM. The role of modification in noradrenergic peripheral pathways after nerve lesions in the generation of pain. P 101. In Fields HL, Liebeskind JC (eds): Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues: Progress in Pain Research and Management. Vol. 1. IASP Press, Seattle, 1994
Cotman CW, Berchtold NC, Christie LA. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends Neurosci. 2007 Sep;30(9):464–72
Zheng F, Zhou X, Moon C, Wang H. Review article: Regulation of brain-derived neurotrophic factor expression in neurons. Int J Physiol Pathophysiol Pharmacol 2012; 4(4):188–200
Mattson MP, Duan W, Wan R, and Guo Z. Prophylactic activation of neuroprotective stress response pathways by dietary and behavioral manipulations. NeuroRx. 2004; 1 No 1: 111–116
Sluka KA, O‘Donnell JM, Danielson J, Rasmussen LA. Regular physical activity prevents development of chronic pain and activation of central neurons. J Appl Physiol 1985; 114(6):725–33
Sluka KA, Danielson J, Rasmussen L, and Dasilva LF. Exercise-induced pain requires NMDA receptor activation in the medullary raphe nuclei. Med Sci Sports Exerc. 2012; 44(3): 420–427
Neves G, Cooke SF, and Bliss TVP. Synaptic plasticity, memory and the hippocampus: a neural network approach to causality. Nature reviews | neuroscience 2008; 9:65–75
Jänig W and Koltzenburg M. What is the interaction between the sympathetic terminal and the primary afferent fiber? P 331. In: Towards a New Pharmacology of Pain. Basbaum AI and Besson JM (eds). Dahlem Workshop Reports, John Wiley and Sons, Chichester, 1991
Jänig W. Koltzenburg M: Possible ways of sympathetic afferent interactions. P 213. In: Reflex Sympathetic Dystrophy: Pathophysiological Mechanisms and Clinical Implications. Jänig W. and Schmidt RF (eds). VCH Verlagsgesellschaft, Weinheim, 1992
Amir S, Brown ZW, and Amit Z. The role of endorphins in stress: Evidence and speculations. Neuroscience & Biobehavioral Reviews 1980; 4:77–86
Schlereth T, Birklein F. The sympathetic nervous system and pain. Neuromolecular Med. 2008;10 No 3:141–7.
Berger, J.M., Katz, R. Sympathetically Maintained Pain. In: The Management of Pain, Ashburn M, and Rice LJ. Editors, Churchill Livingstone Inc, 1997
Wahren LK, Torebjörk E, Nyström, B: Quantitative sensory testing before and after regional guanethidine block in patients with neuralgia in the hand. Pain 1991; 46:23–30
Koltzenburg M, Torebjörk HE, and Wahren LK: Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain. Brain 1994; 117:579
Veldman PHJM, Reynen HM, Arntz IE, and Goris RJA: Signs and symptoms of reflex sympathetic dystrophy: prospective study of 829 patients. The Lancet 1993; 342:1012
Meller ST, and Gebhart GF: Spinal Mediators of Hyperalgesia Drugs 1994; 47 suppl. 5:10–20
Wallin BG, Torebjörk HE, and Hallin RG: Preliminary observations on the pathophysiology of hyperalgesia in the causalgic pain syndrome. P 489. In: Sensory Functions of the Skin in Primates. Zotterman Y (ed). Pergamon Press, Oxford, 1976
McLachlan EM, Jänig W, Devor M, and Michaelis M. Peripheral nerve injury triggers noradrenergic sprouting within dorsal root ganglia. Nature 363:543, 1993
Jänig W, McLachlan E: On the fate of sympathetic and sensory neurons projecting into a neuroma of the superficial peroneal nerve in the cat. J Comp Neurol 225:302, 1984
Devor M and Woll PD. Cross-excitation in dorsal root ganglia of nerve-injured and intact rats. J Neurophysiol 1990; 64:1733
Campbell JN, Meyer RA, and Raja SN. Is nociceptor activation by alpha-1-adrenoreceptors the culprit in sympathetically maintained pain? Am Pain Soc J. 1992:1:3–11
Perl ER: A reevaluation of mechanisms leading to sympathetically related pain. In: Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues: Progress in Pain Research and Management. Vol. 1. Fields HL, Liebeskind JC (eds). IASP Press, Seattle, 1994
Ossipov MH, Dussor GO, and Porreca P. Central modulation of pain. J Clin Invest. 2010; 120 (11): 3779–3787
Heinricher MM, Morgan MM, Tortorici V, and Fields HL. Direct and indirect actions of morphine on medullary neurons that modulate nociception. Neuroscience 1992; 48 No. 3: 533–543
Hermann DM, Luppi P-H, Peyron C, and Hinkle P et al. Afferent projections to the rat nuclei raphe magnus, raphe pallidus and reticularis gigantocellularis pars demonstrated by iontophoretic application of choleratoxin (subunit b). Journal of Chemical Neuroanatomy 1997; 13 No 1:1–21
Stamford JA. Descending control of pain. BJA 1995; 75: 217–27
Fields HL, Heinricher MM, and Mason P. Neurotransmitters in nociceptive modul atory circuits. Annu. Rev. Neurosci. 1991. 14:219–45
Fields HL et al Bonica 2001 Bonica JJ, Loeser JD, Chapter 1: History of pain concepts and therapies. In: Bonica’s Management of Pain, third edition: Loeser JD et al editors, Lippincott Williams & Wilkins, Philadelphia, 2001
Fields HL, Malick A, and Burstein R. Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial medulla. J Neurophysiol. 1995; 74 No 4:1742–59
Morgan MM, Whittier KL, Hegarty DM, and Aicher SA. Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla. Neurological Sciences Pain. 2008; 140 No 2: 376–386
Heinricher MM, Tavaresc I, Leithe JL, and Lumbe B.M. Descending control of nociception: Specificity, recruitment and plasticity Brain research reviews 2009; 60: 214–225
Heinricher MM, Schoutena JC, and Jobstb EE. Activation of brainstem N-methyl-d-aspartate receptors is required for the analgesic actions of morphine given systemically. Pain 2001; 92: 129–138
Heinricher MM, Morgan MM, Tortorici V, and Fields HL. Disinhibition of off-cells and antinociception produced by an opioid action within the rostral ventromedial medulla. Neuroscience 1994; 63 No 1: 279–288
Marinelli S, Vaughan CW, Schnell SA, Wessendorf MW, et al. Rostral ventromedial medulla neurons that project to the spinal cord express multiple opioid receptor phenotypes. The Journal of Neuroscience 2002; 2(24):10847–10855
Hermann, DM, Luppi PH, Peyron C, Hinckel P, and Jouvet M. Afferent projections to the rat nuclei raphe magnus, raphe pallidus and reticularis gigantocellularis pars demonstrated by iontophoretic application of choleratoxin (subunit b). Journal of Chemical Neuroanatomy 1997; 13 No 1: 1–21
Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science 2000; 288: 1769–1772
Peyron R, Laurant B, Garcia-Larrea L. Functional imaging of brain responses to pain: A review and meta-analysis. Neurophysiologie Clinique/Clinical Neurophysiology 2000; 30 No 5:263–288
Siddall PJ and Cousins MJ. Introduction to pain mechanisms: implications for neural blockade. Chapter 23.1. In: Neural Blockade In Clinical Anesthesia and Management of Pain: 3 rd Ed. Cousins MJ and Bridenbaugh PO editors. Lippencott-Raven, Philadelphia 1998
Sullivan MJL. Toward a biopsychomotor conceptualization of pain: Implications for research and intervention. Clin J Pain 2008;24:281–290 70. Watson DE and Williams BO. Eccles’ model of the self controlling its brain. NeuroQuantology 2003; 1: 119–128
Eccles JC. A unitary hypothesis of mind-brain interaction in the cerebral cortex. Proc Roy Soc London B 1990;240: 433–451
Eccles JC. How the Self Controls its Brain. Berlin: Springer-Verlag. 1994
Beck, F., and Eccles, J., , “Quantum aspects of brain activity and the role of consciousness.”Proceedings of the National Academy of Sciences of the USA 1992; 89: 11357–11361
Cox JJ, Reimann F, Nicholas AK, Thornton G, et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006; 444 (7121): 894–8
Tau G and Peterson B. Normal development of brain circuits. Neuropsychopharmacology 2010; 35(1): 147–168
Borsook D, Edwards R, Elman I, Becerra L, and Levine J. Pain and analgesia: The value of salience circuits. Progress in Neurobiology 2013; 104: 93–105
Grzisiak RC. Revisiting pain-prone personalities: Combining psychodynamics with neurobiological sequelae of trauma. AJPM 2003; 13 No 1:6-15
Collin SHP, Milivojevic B, Doeller CF. Memory hierarchies map onto the hippocampal long axis in humans. Nature Neuroscience 2015; 18:1562–1564
Kim D, Pare´ D, and Nair SS. The assignment of model amygdola neurons to the fear memory trace depends on competitive synaptic interactions. Journal of Neuroscience 2013; 33 No 36:14354–14358
Verney TR. What cells remember: Toward a unified field theory of memory. Journal of Prenatal & Perinatal Psychology & Health 2014; 29 No 1:16-29 81.
Kandel ER. The molecular biology of memory storage: A dialogue between genes and synapses. Nobel Lecture, December 8, 2000
Wedden V and Wald LL. Martinos Center for Biomedical Imaging, Human Connectome Project
Chapman CR, Tuckett RP, and Song CW. Pain and stress in a systems perspective: Reciprocal neural, endocrine, and immune interactions. J of Pain 2008; 9 No 2:122-45
Bernstein B, Stamatoyannopoulos J, Costello J, Ren B, Aleksandar A, et al. The NIH roadmap epigenomics mapping consortium. Nat Biotechnol. 2010; 28 No 10: 1045–1048
Bell CG and Beck S. The epigenomic interface between genome and environment in common complex diseases. Briefings in functional genomics. 2010; 9 No 6: 477–485
Twaroski DM, Yan Y, Olson JM, Bosnjak ZJ, and Bai X. Down-regulation of microRNA-21 is involved in the propofol-induced neurotoxicity observed in human stem cell–derived neurons. Anesthesiology 2014; 121:786-800
Lutz ML, Bekker A, and Tao YX. Noncoding RNAs, new players in chronic pain. Anesthesiology 2014; 121:409-17
Mattson MP, Duan W, Wan R, and Guo Z. Prophylactic Activation of Neuroprotective Stress Response Pathways by Dietary and Behavioral Manipulations NeuroRx. 2004 Jan; 1 No1: 111–116
Stiles J, Jernigan TL. The basics of brain development. Neuropsychol Rev. 2010; 20 No 4: 327–348 90. Atmanspacher H. "Quantum Approaches to Consciousness", The Stanford Encyclopedia of Philosophy (summer 2015 Edition), Edward N. Zalta (ed.), URL = <http://plato.stanford.edu/archives/sum2015/entries/qt-consciousness/>.
Mandal A. MD Medical News: Life Sciences & Medicine February 11, 2016
Chavez CM, McGaugh JM, and Weinberger NM. Activation of the basolateral amygdala induces long-term enhancement of specific memory representations in the cerebral cortex. Neurobiology of Learning and Memory 2013; 101: 8–18
McGaugh J L. Involvement of hormonal and neuromodulatory systems in the regulation of memory storage. Annual Review of Neuroscience 1989; 12, 255– 287
McGaugh J L. Memory-A century of consolidation. Science. 2000; 287(5451), 248–251)
McGaugh J L. Memory consolidation and the amygdala: A systems perspective. Trends in Neurosciences 2002; 25 No 9: 456–461
McGaugh J L. Memory and Emotion: The Making of Lasting Memories. Columbia University Press, New York 2003
McGaugh J L. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annual Review of Neuroscience 2004; 27: 1–28
McGaugh J L and Roozendaal B. Drug enhancement of memory consolidation: Historical perspective and neurobiological implications. Psychopharmacology 2009; 202(1–3):3–14
BodyMaps. Healthline Medical Team; April 14, 2015. http://www.healthline. com/human-body-maps/hippocampus
McCaffrey P. Chapter 6. The midbrain, pons, medulla and reticular formation. In: Neuroscience on the Web Series CMSD Neuroanatomy of Speech, Swallowing, and Language http://www.csuchico.edu/~pmccaffrey/syllabi/CMSD%20 320/362unit6.html
https://www.google.com/search?q=hippocampus&biw=1242&bih=58 5&tbm=isch&imgil=dRbk0nHmLeDMwM%253A%253B_Vo-VkSdOHi6M%253Bhttp%25
The Reticular Formation (Integrative Systems) Part 2 What-When-How; In Depth Tutorials and Information. http://what-when-how.com/neuroscience/ the-reticular-formation-integrative-systems-part-2/
Wilcox CE, Mayer AR, Teshiba TM, Ling J, et al. The subjective experience of pain: An FMRI study of percept-related models and functional connectivity. Pain Medicine 2015; 16:2121-33
Peyron R, Laurent B, Garca-Larrea L. Functional imaging of brain responses to pain: A review and meta-analysis Neurophysiologie Clinique/Clinical Neurophysiology 2000; 30 No 5:263–288
Woolf CJ, Shortland P, Coggeshall RE. Peripheral Nerve Injury Triggers Central Sprouting of Myelinated Afferents. Nature 1992; 355(6355):75–78
Mannion RJ and Woolf CJ. Pain mechanisms and management:A central perspective. Clin J Pain 2000; 16:S144–S156
Mannion RJ, Doubell TP, Coggeshall RE, and Woolf CJ. Collateral sprouting of uninjured primary afferent A-fibers into the superficial dorsal horn of the adult rat spinal cord after topical capsaicin treatment to the sciatic nerve. Journal of Neuroscience 1996; 16 No 16:5189–5195
Hughes DI, Scott DT, Todd AJ, and Riddell JS. Lack of evidence for sprouting of A afferents into the superficial laminas of the spinal cord dorsal horn after nerve section. The Journal of Neuroscience 2003; 23 No 29: 9491–9499
Harris JA, Corsi M, Quartaroli M, Arban R, and Bentivoglio M. Up regulation of spinal glutamate receptors in chronic pain. Neuroscience 1996; 74: 7–12
Moore KA, Kohno T, Karchewski LA, Scholz J, Baba H, and Woolf CJ. Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci 2002; 22: 6724–6731
Shin S-W and Eisenach JC. Peripheral nerve injury sensitizes the response to visceral distension but not its inhibition by the antidepressant milnacipran. Anesthesiology 2004; 100 No 3:671–675
Latremoliere A. and Woolf CJ. Central sensitization: A generator of pain hypersensitivity by central neural plasticity. Journal of Pain 2009; 10 No 9: 895–926
Ji RR, Kohno T, Moore KA, and Woolf CJ. Central sensitization and long term potentiation (LTP): Do pain and memory share similar mechanisms? Trends Neurosci. 2003; 26 No 12:696–705
Groveman B. Novel mechanisms underlying the regulation of SRC kinase in the regulation of NMDA receptor SRC signaling complex. Ph.D. dissertation 2011, Florida State University College of Medicine
Rivat C, Laboureyras E, Laulin J-P, Le Roy C, Richeb P, and Simonnet G. Nonnociceptive environmental stress induces hyperalgesia, not analgesia, in pain and opioid-experienced rats. Neuropsychopharmacology 2007; 32:2217–2228
Brodal A: Neurological Anatomy in Relation to Clinical Medicine, 3rd ed. Oxford University Press, New York, 1981
Elliott KJ. Taxonomy and mechanisms of neuropathic pain. Seminars in Neurology 1994;14 No.3:195–205
Besson JM and Charouch A. Peripheral and spinal mechanisms of nociception. Physiol Rev 1988; 67: 167–186 Cook AJ, Woolf CJ, Wall PD, and McMahon SB. Dynamic receptive field plasticity in rat spinal dorsal horn following c-fiver primary afferent input. Nature 1987; 325:151–153
Duggan AW and Johnston GAR. Glutamate and related amino acids in cat spinal cords, dorsal root ganglion and peripheral nerves. J. Neurochem 1970; 17:12051208
Lipton SA, Rosenberg PA: Mechanisms of disease: review article. NEJM 1994; 330 No 9:613–622 123. Nakanishi S: Molecular diversity of glutamate receptors and implications for brain function. Science 1986; 258(5082): 597–603 McDermott A B, Mayer M L, Westbrook G L, Smith SJ, and Barker JL. NMDAreceptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurons. Nature 1986; 321: 519– 522
Papadia S and Hardingham GE. The dichotomy of NMDA receptor signaling. Neuroscientist. 2007; 13 No 6: 572–579
Mayer DJ, Mao J, Price DD. The development of morphine tolerance and dependence is associated with translocation of protein kinase. PAIN 1995; 61(3):365–74
Mao J, Price DD, and Mayer DJ. Mechanisms of hyperalgesia and morphine tolerance: a current view of their possible interactions. Pain 1995; 62: 259-274
MacDonald JF, Novak LM: Mechanisms of blockade of excitatory amino acid receptor channels. Trends Pharmacol 1990; 11:167–172
Brookoff D. Chronic pain: 1. A new disease? Hospital Practice 2000; 35 No 7: 45–59
Mayer D, Mao J, Holt J, and Price DD. Cellular mechanisms of neuropathic pain, morphine tolerance and their interactions. Proc, Natl Acad. Sci. USA 1999; 96:7731–7736
Bean BP: Classes of calcium channels in vertebrate cells. Annual Rev Physiol. 1989; 51:367–84
Dickenson AH. NMDA receptor antagonists as analgesics. P 173. In: Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues: Progress in Pain Research. Vol 1. Fields HL, Liebeskind JC (eds): IASP Press, Seattle, 1994
Dickenson AH and Sullivan AF: Evidence for a role of the NMDA receptor in the frequency dependent potentiation of deeper dorsal horn neurons following c-fiber stimulation. Neuropharmacol 1987; 26:1235–1238
Dickenson AH and Sullivan AF: Differential effects of excitatory amino-acid antagonists on dorsal horn nociceptive neurons in the rat. Brain Res 1990; 506:31–39
Tan YH, Li K, Chen XY, Cao Y, et al. Activation of Src family kinases in spinal microglia contributes to formalin-induced persistent pain state through p38 pathway. The Journal of Pain 2012; 13, No 10:1008–1015
Manzerra P, Behrens MM, Canzoniero LM, Wang XQ, et al. Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity. Proc Natl Acad Sci USA 2001; 98:11055–11061
Viviani B, Bartesaghi S, Gardoni F, Vezzani A, et al. Interleukin-1 enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. The Journal of Neuroscience 2003; 23 No 25:8692– 8700
Groveman BR, Feng S, Fang XQ, Pflueger M, et.al. The regulation of N-methyl-Daspartate receptors by Src kinase. FEBS Journal 2012; 279: 20–28
Salter MW and Kalia LV. Src kinases: a hub for NMDA receptor regulation. Nature Reviews Neuroscience 2004; 5:317–328
Dickenson AH and Sullivan AF. Differential effects of excitatory amino-acid antagonists on dorsal horn nociceptive neurons in the rat. Brain Res 1990; 506:31–39
Costigan M, Scholz J, and Woolf CJ. Neuropathic pain: A maladaptive response of the nervous system to damage. Annu. Rev. Neurosci. 2009. 32:1–32
Tamura R, Nemoto T, Maruta T, Onizuka S, et al. Up-regulation of NaV1.7 sodium channels expression by tumor necrosis factor- in cultured bovine adrenal chromaffin cells and rat dorsal root ganglion neurons. Anesth and Analg. 2014; 118 No 2: 318–24
Thompson SWN, Woolf CJ: Primary afferent-evoked prolonged potentials in the spinal cord and their central summation: role of the NMDA receptor. P 291. In: Proceedings VIth World Congress on Pain. Bond MR, Charlton JE, and Woolf CJ (eds) Elsevier, Amsterdam, 1991)
Price DD, Mao J, and Mayer DJ: Central neural mechanisms and abnormal pain states. P. 61. In: Pharmacological Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues: Progress in Pain Research and Management. Vol. 1. Fields HL and Liebeskind JC (eds): IASP Press, Seattle, 1994
Kelstein DE, Price DD, Hayes RL, and Mayer DJ: Evidence that substance P selectively modulates C-fiber evoked discharges of dorsal horn nociceptive neurons. Brain Res 1990; 526:291–298
Himmelseher S and Durieux ME. Ketamine for perioperative pain management. Anesthesiology 2005; 102:211–20
Kelstein DE, Price DD, Hayes RL, and Mayer DJ: Evidence that substance P selectively modulates C-fiber evoked discharges of dorsal horn nociceptive neurons. Brain Res 1990; 526:291–298
Meller ST and Gebhart GF: Nitric oxide (NO) and nociceptive processing in the spinal cord. Pain 1993;52:127–36
Woolf, CJ: A new strategy for the treatment of inflammatory pain. Drugs 1994; 47 (suppl. 5):1–9.
Woolf CJ and Chong MS: Preemptive analgesia-treating postoperative pain by preventing the establishment of central sensitization: review articles. Anesth Analg 1993; 77:362–379
Dickenson AH. Spinal cord pharmacology of pain. BJA 1995;75:193-200 152. Naranjo JR, Millstrom B, Achaval M, Sassone-Corsi P. Molecular pathways of pain: Fos/Jun-mediated activation of a noncanomical AP-1 site in the prodynorphin gene. Neuron. 1991; 6 No 4:607–617
Elliott KJ, Brodsky M, Hynansky, AD, Foley KM, and Inturrisi CE.
Dextromethorphan suppresses both formalin-induced nociceptive behavior and the formalin-induce increase in spinal cord c-fos mRNA. Pain 1995; 61:401-9
Bredt DS, Snyder SH. Nitric oxide: a novel neuronal messenger. Neuron 1992; 8 No 1:3–11
Dawson VL, Dawson TM, London ED et al: Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc Natl Acad Sci USA 1991; 88:6368-6371
Sorkin L. NMDA evokes an L-NAME sensitive spinal release of glutamate and citrulline. NeuroReport 1993; 4: 479–482
Draisci G and Ladarda MJ. Temporal analysis of increases in c-fos, preprodynorphin and preproenkephalin mRNAs in rat spinal cord. Mol Brain Res 1989; 6:31–37
Gogas KR, Presley RW, Levine JD, and Basbaum AI. The antinociceptive action of supraspinal opioids results from an increase in descending inhibitory control: correlation of nociceptive behavior and c-fos expression. Neuroscience 1990; 10: 323–33.
Presley RW, Menetry D, Levine JD, and Basbaum AI. Systemic morphine suppresses noxious stimulation-evoked for protein-like immunoreactivity in the rat spinal cord. Neuroscience 10:323, 1990
Stanfa LC, Sullivan AF, and Dickensen AH. Increased potency of spinal opiates after peripheral inflammation in the halothane anesthetized rat. Pain 1992; 50: 345–54
Chen L and Huang LYM. Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a mu-opioid. Neuron 1991; 7: 319–326.
Chen L, Huang LYM: Protein Kinase C reduces MG2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 1992; 356(6369):521–3
Apkarian AV, Sosa Y, Sonty S, Levy RM, et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. The Journal of Neuroscience, 2004; 24(46):10410–10415
Mayer D, Mao J, Holt J, et al. Cellular mechanisms of neuropathic pain, morphine tolerance and their interactions. Proc, Natl Acad. Sci. USA 1999; 96:7731-7736
Stein C., Comisel K, Haimerl E, et al, Analgesic effect of intra-articular morphine after arthroscopic surgery. NEJM 1991; 325: 1123–6
Likaar R, Schafer M, Paulak F., et al. Intra-articular morphine analgesia in chronic pain patients with osteoarthritis. Anesth Analg 1997; 84:1313-7) (Stein C. Mechanisms of disease: The control of pain in peripheral tissue by opioids. NEJM 332:1685–90
Kao JX, Xu Xj, Yu YX, Seiger A, et al. Baclofen reverses the hypersensitivity of dorsal horn wide dynamic range neurons to mechanical stimulation after transient spinal cord ischemia: implications for a tonic GABAergic inhibitory control of myelinated fiber input. J. Neurophysiol 1992; 68:392–396
Kapitzke D, Vetter I, and Cabot PJ. Endogenous opioid analgesia in peripheral tissues and the clinical implications for pain control. Therapeutics and Clinical Risk Management 2005; 1 No 4 : 279–297
Choi DW. Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neurosci Lett 1985; 58:293–297.
Obreja O, Ringkamp M, Turnquist B, Hirth M, et al. Nerve growth factor selectively decreases activity-dependent conduction slowing in mechanoinsensitive C-nociceptors. Pain; 2011;152 No 9:2138–46
Prencipe G, Minnone G, Strippoli R, De Pasquale L, et al. Nerve growth factor down regulates inflammatory response in human monocytes through TrkA. J Immunol. 2014 Apr 1;192 No 7: 3345–54
Mantyh PW, Koltzenburg M, Mendell LM, Tive L, and Shelton DL. Antagonism of nerve growth factor-TrkA signaling and the relief of pain. Anesthesiology 2011; 115 No 1: 189–204
Mcmahon SB, Bennett DLH, Priestley JV, and Shelton DL. The biological effects of endogenous nerve growth factor on adult sensory neurons revealed by a trkA-IgG fusion molecule. Nature Medicine 1995; 1:774–780
Munoz M. and Covenas R. NK-1 receptor antagonists: a new paradigm in pharmacological therapy. Curr Med Chem. 2011; 18 No 12: 1820–31 175.
Smith HS, Smith JM, and Seidner P. Opioid-induced nausea and vomiting. Ann Palliat Med 2012;1 No 2:121–129
Fromm GH. Baclofen as an adjuvant analgesic. Journal of Pain and Symptom Management 1994; 9 No. 8:500–509
Staud R, Michael E, Robinson ME, and Price DD. Temporal summation of second pain and its maintenance are useful for characterizing widespread central sensitization of fibromyalgia patients, J Pain. 2007; 8 No 11: 893–901
Laroche S. Cellular and molecular approaches to memory storage. Therapie, 2000; 55:461–466
Walther W, and Stein U. Viral vectors forё gene transfer: a review of their use in the treatment of human diseases. Drugs. 2000; 60 No 2: 249–71
Nadel L, Hupbach A, Gomez R, and Newman-Smith K. Memory formation, consolidation and transformation. J Neuroscience and Behavioral Review 2012; 36:1640–1645
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