Skip to main content
Erschienen in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 2/2014

01.02.2014 | Review Article/Brief Review

The transition from acute to chronic pain: understanding how different biological systems interact

verfasst von: Katherine A. Mifflin, BSc, Bradley J. Kerr, PhD

Erschienen in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Although pain is an adaptive sensory experience necessary to prevent further bodily harm, the transition from acute to chronic pain is not adaptive and results in the development of a chronic clinical condition. How this transition occurs has been the focus of intense study for some time. The focus of the current review is on changes in neuronal plasticity as well as the role of immune cells and glia in the development of chronic pain from acute tissue injury and pain.

Principal findings

Our understanding of the complex pathways that mediate the transition from acute to chronic pain continues to increase. Work in this area has already revealed the complex interactions between the nervous and immune system that result in both peripheral and central sensitization, essential components to the development of chronic pain. Taken together, a thorough characterization of the cellular mechanisms that generate chronic pain states is essential for the development of new therapies and treatments. Basic research leading to the development of new therapeutic targets is promising with the development of chloride extrusion enhancers. It is hoped that one day they will provide relief to patients with chronic pain.

Conclusions

A better understanding of how chronic pain develops at a mechanistic level can aid clinicians in treating their patients by showing how the underlying biology of chronic pain contributes to the clinical manifestations of pain. A thorough understanding of how chronic pain develops may also help identify new targets for future analgesic drugs.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Loeser, JD, Treede, RD. The Kyoto protocol of IASP basic pain terminology. Pain 2008; 473-7. Loeser, JD, Treede, RD. The Kyoto protocol of IASP basic pain terminology. Pain 2008; 473-7.
2.
Zurück zum Zitat Moriarty O, McGuire BE, Finn DP. The effect of pain on cognitive function: A review of clinical and preclinical research. Prog Neurobiol 2011; 93: 385-404.PubMedCrossRef Moriarty O, McGuire BE, Finn DP. The effect of pain on cognitive function: A review of clinical and preclinical research. Prog Neurobiol 2011; 93: 385-404.PubMedCrossRef
3.
Zurück zum Zitat Institute of Medicine Committee on Advancing pain research, Care, and Education. Relieving Pain in America: A blueprint for transforming prevention, care, education, and research. Nat Acad Press; 2011. Institute of Medicine Committee on Advancing pain research, Care, and Education. Relieving Pain in America: A blueprint for transforming prevention, care, education, and research. Nat Acad Press; 2011.
4.
Zurück zum Zitat Moulin DE, Clark AJ, Speechley M, Morley-Forster PK. Chronic pain in Canada-Prevalence, treatment, impact, and the role of opioid analgesia. Pain Res Manag 2002; 7: 179-84.PubMed Moulin DE, Clark AJ, Speechley M, Morley-Forster PK. Chronic pain in Canada-Prevalence, treatment, impact, and the role of opioid analgesia. Pain Res Manag 2002; 7: 179-84.PubMed
5.
Zurück zum Zitat Sherman RA, Sherman CJ, Parker L. Chronic phantom and stump pain among American veterans: results of a survey. Pain 1984; 18: 83-95.PubMedCrossRef Sherman RA, Sherman CJ, Parker L. Chronic phantom and stump pain among American veterans: results of a survey. Pain 1984; 18: 83-95.PubMedCrossRef
6.
Zurück zum Zitat Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983; 306: 686-8.PubMedCrossRef Woolf CJ. Evidence for a central component of post-injury pain hypersensitivity. Nature 1983; 306: 686-8.PubMedCrossRef
7.
Zurück zum Zitat Finnerup NB, Sørensen L, Biering-Sørensen F, Johannesen IL, Jensen TS. Segmental hypersensitivity and spinothalamic function in spinal cord injury pain. Exp Neurol 2007; 207: 139-49.PubMedCrossRef Finnerup NB, Sørensen L, Biering-Sørensen F, Johannesen IL, Jensen TS. Segmental hypersensitivity and spinothalamic function in spinal cord injury pain. Exp Neurol 2007; 207: 139-49.PubMedCrossRef
8.
Zurück zum Zitat Woolf CJ, Wall PD. Relative effectiveness of C primary afferent fibers of different origins in evoking a prolonged facilitation of the flexor reflex in the rat. J Neurosci 1986; 6: 1433-42.PubMed Woolf CJ, Wall PD. Relative effectiveness of C primary afferent fibers of different origins in evoking a prolonged facilitation of the flexor reflex in the rat. J Neurosci 1986; 6: 1433-42.PubMed
9.
Zurück zum Zitat Detloff MR, Fisher LC, McGaughy V, Longbrake EE, Popovich PG, Basso DM. Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol 2008; 212: 337-47.PubMedCentralPubMedCrossRef Detloff MR, Fisher LC, McGaughy V, Longbrake EE, Popovich PG, Basso DM. Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol 2008; 212: 337-47.PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Samad TA, Moore KA, Sapirstein A, et al. Interleukin-1B-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 2001; 410: 471-5.PubMedCrossRef Samad TA, Moore KA, Sapirstein A, et al. Interleukin-1B-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature 2001; 410: 471-5.PubMedCrossRef
11.
Zurück zum Zitat Ma QP, Woolf CJ. Progressive tactile hypersensitivity: an inflammatory-induced incremental increase in the excitability of the spinal cord. Pain 1996; 67: 97-106.PubMedCrossRef Ma QP, Woolf CJ. Progressive tactile hypersensitivity: an inflammatory-induced incremental increase in the excitability of the spinal cord. Pain 1996; 67: 97-106.PubMedCrossRef
12.
Zurück zum Zitat Shubayev VI, Angert M, Dolkas J, Campana WM, Palenscar K, Myers RR. TNFα-induced MMP-9 promotes macrophage recruitment into injured peripheral nerve. Mol Cell Neurosci 2006; 31: 407-15.PubMedCrossRef Shubayev VI, Angert M, Dolkas J, Campana WM, Palenscar K, Myers RR. TNFα-induced MMP-9 promotes macrophage recruitment into injured peripheral nerve. Mol Cell Neurosci 2006; 31: 407-15.PubMedCrossRef
13.
Zurück zum Zitat Ji SX, Zhuang ZY, Woolf CJ, Ji RR. p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci 2003; 23: 4017-22.PubMed Ji SX, Zhuang ZY, Woolf CJ, Ji RR. p38 mitogen-activated protein kinase is activated after a spinal nerve ligation in spinal cord microglia and dorsal root ganglion neurons and contributes to the generation of neuropathic pain. J Neurosci 2003; 23: 4017-22.PubMed
14.
Zurück zum Zitat Kim D, Kim MA, Cho IH, et al. A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. J Biol Chem 2007; 282: 14975-83.PubMedCrossRef Kim D, Kim MA, Cho IH, et al. A critical role of toll-like receptor 2 in nerve injury-induced spinal cord glial cell activation and pain hypersensitivity. J Biol Chem 2007; 282: 14975-83.PubMedCrossRef
15.
Zurück zum Zitat Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol 2005; 5: 629-40.PubMedCrossRef Allan SM, Tyrrell PJ, Rothwell NJ. Interleukin-1 and neuronal injury. Nat Rev Immunol 2005; 5: 629-40.PubMedCrossRef
16.
Zurück zum Zitat Guenther S, Reeh PW, Kress M. Rises in [Ca2+]i mediate capsaicin-and proton-induced heat sensitization of rat primary nociceptive neurons. Eur J Neurosci 1999; 11: 3143-50.PubMedCrossRef Guenther S, Reeh PW, Kress M. Rises in [Ca2+]i mediate capsaicin-and proton-induced heat sensitization of rat primary nociceptive neurons. Eur J Neurosci 1999; 11: 3143-50.PubMedCrossRef
17.
Zurück zum Zitat Walder R, Radhakrishnan R, Loo L, et al. TRPV1 is important for mechanical and heat sensitivity in uninjured animals and development of heat hypersensitivity after muscle inflammation. Pain 2012; 153: 1664-72.PubMedCentralPubMedCrossRef Walder R, Radhakrishnan R, Loo L, et al. TRPV1 is important for mechanical and heat sensitivity in uninjured animals and development of heat hypersensitivity after muscle inflammation. Pain 2012; 153: 1664-72.PubMedCentralPubMedCrossRef
18.
Zurück zum Zitat Chuang HH, Prescott ED, Kong H, et al. Bradykinin and nerve growth factor release the caspsaicin receptor from PtdIns(4, 5)P2-mediated inhibition. Nature 2001; 411: 957-62.PubMedCrossRef Chuang HH, Prescott ED, Kong H, et al. Bradykinin and nerve growth factor release the caspsaicin receptor from PtdIns(4, 5)P2-mediated inhibition. Nature 2001; 411: 957-62.PubMedCrossRef
19.
Zurück zum Zitat Gold MS, Levine JD, Correa AM. Modulation of TTX-R INa by PKC and PKA and their role in PGE2-induced sensitization of rat sensory neurons in vitro. J Neurosci 1998; 18: 10345-55.PubMed Gold MS, Levine JD, Correa AM. Modulation of TTX-R INa by PKC and PKA and their role in PGE2-induced sensitization of rat sensory neurons in vitro. J Neurosci 1998; 18: 10345-55.PubMed
20.
Zurück zum Zitat Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ. P38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 2002; 36: 57-68.PubMedCrossRef Ji RR, Samad TA, Jin SX, Schmoll R, Woolf CJ. P38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron 2002; 36: 57-68.PubMedCrossRef
21.
Zurück zum Zitat Fischer MJ, Btesh J, McNaughton PA. Disrupting sensitization of transient receptor potential vanilloid subtype 1 inhibits inflammatory hyperalgesia. J Neurosci 2013; 33: 7407-14.PubMedCrossRef Fischer MJ, Btesh J, McNaughton PA. Disrupting sensitization of transient receptor potential vanilloid subtype 1 inhibits inflammatory hyperalgesia. J Neurosci 2013; 33: 7407-14.PubMedCrossRef
22.
Zurück zum Zitat Banik RK, Brennan TJ. Trpv1 mediates spontaneous firing and heat sensitization of cutaneous primary afferents after plantar incision. Pain 2009; 141: 41-51.PubMedCentralPubMedCrossRef Banik RK, Brennan TJ. Trpv1 mediates spontaneous firing and heat sensitization of cutaneous primary afferents after plantar incision. Pain 2009; 141: 41-51.PubMedCentralPubMedCrossRef
23.
Zurück zum Zitat Carreira EU, Carregaro V, Teixeira MM, et al. Neutrophils recruited by CXCR1/2 signalling mediate post-incisional pain. Eur J Pain 2013; 17: 654-63.PubMedCrossRef Carreira EU, Carregaro V, Teixeira MM, et al. Neutrophils recruited by CXCR1/2 signalling mediate post-incisional pain. Eur J Pain 2013; 17: 654-63.PubMedCrossRef
24.
Zurück zum Zitat Cunha TM, Barsante MM, Guerrero AT, et al. Treatment with DF 2162, a non-competitive allosteric inhibitor of CXCR1/2, diminishes neutrophil influx and inflammatory hypernociception in mice. Br J Pharmacol 2008; 154: 460-70.PubMedCrossRef Cunha TM, Barsante MM, Guerrero AT, et al. Treatment with DF 2162, a non-competitive allosteric inhibitor of CXCR1/2, diminishes neutrophil influx and inflammatory hypernociception in mice. Br J Pharmacol 2008; 154: 460-70.PubMedCrossRef
25.
Zurück zum Zitat Cunha TM, Verri WA Jr, Schivo IR, et al. Crucial role of neutrophils in the development of mechanical inflammatory hypernociception. J Leukoc Biol 2008; 83: 824-32.PubMedCrossRef Cunha TM, Verri WA Jr, Schivo IR, et al. Crucial role of neutrophils in the development of mechanical inflammatory hypernociception. J Leukoc Biol 2008; 83: 824-32.PubMedCrossRef
26.
Zurück zum Zitat Ramon CD, Fernandes KS, Canetti C, Teixeira MM, Silva JS, Cunha FQ. Neutrophil recruitment in immunized mice depends on MIP-2 inducing the sequential release of MIP-1alpha, TNFalpha and FTB(4). Eur J Immunol 2006; 36: 2025-34.CrossRef Ramon CD, Fernandes KS, Canetti C, Teixeira MM, Silva JS, Cunha FQ. Neutrophil recruitment in immunized mice depends on MIP-2 inducing the sequential release of MIP-1alpha, TNFalpha and FTB(4). Eur J Immunol 2006; 36: 2025-34.CrossRef
27.
Zurück zum Zitat Guerrero AT, Verri WA Jr, Cunha TM, et al. Involvement of LTB4 in zymosan-induced joint nociception in mice: participation of neutrophils and PGE2. J Leukoc Biol 2008; 83: 122-30.PubMedCrossRef Guerrero AT, Verri WA Jr, Cunha TM, et al. Involvement of LTB4 in zymosan-induced joint nociception in mice: participation of neutrophils and PGE2. J Leukoc Biol 2008; 83: 122-30.PubMedCrossRef
28.
Zurück zum Zitat Zhang J, De Koninck Y. Spatial and temporal relationship between monocyte chemoattractant protein-1 expression and spinal glial activation following peripheral nerve injury. J Neurochem 2006; 97: 772-83.PubMedCrossRef Zhang J, De Koninck Y. Spatial and temporal relationship between monocyte chemoattractant protein-1 expression and spinal glial activation following peripheral nerve injury. J Neurochem 2006; 97: 772-83.PubMedCrossRef
29.
Zurück zum Zitat Perrin FE, Lacroix S, Avilés-Triqueros M, David S. Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and interleukin-1beta in Wallerian degeneration. Brain 2005; 128: 854-66.PubMedCrossRef Perrin FE, Lacroix S, Avilés-Triqueros M, David S. Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and interleukin-1beta in Wallerian degeneration. Brain 2005; 128: 854-66.PubMedCrossRef
30.
Zurück zum Zitat Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 2003; 3: 745-56.PubMedCrossRef Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 2003; 3: 745-56.PubMedCrossRef
31.
Zurück zum Zitat Carroll SL, Miller ML, Frohnert PW, Kim SS, Corbett JA. Expression of neuregulins and their putative receptors ErbB2 and ErbB3, is induced during Wallerian degeneration. J Neurosci 1997; 17: 1642-59.PubMed Carroll SL, Miller ML, Frohnert PW, Kim SS, Corbett JA. Expression of neuregulins and their putative receptors ErbB2 and ErbB3, is induced during Wallerian degeneration. J Neurosci 1997; 17: 1642-59.PubMed
32.
Zurück zum Zitat Zochodne DW, Levy D, Zwiers H, et al. Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected peripheral nerves. Neurosci 1999; 91: 1515-27.CrossRef Zochodne DW, Levy D, Zwiers H, et al. Evidence for nitric oxide and nitric oxide synthase activity in proximal stumps of transected peripheral nerves. Neurosci 1999; 91: 1515-27.CrossRef
33.
Zurück zum Zitat Verge GM, Milligan ED, Maier SF, Watkins LR, Naeve GS, Foster AC. Fractalkine (CX3CL1) and fractalkine receptors (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Eur J Neurosci 2004; 20: 1150-60.PubMedCrossRef Verge GM, Milligan ED, Maier SF, Watkins LR, Naeve GS, Foster AC. Fractalkine (CX3CL1) and fractalkine receptors (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Eur J Neurosci 2004; 20: 1150-60.PubMedCrossRef
34.
Zurück zum Zitat White FA, Sun J, Waters SM, et al. Excitatory monocyte chemoattractant protein-1 signalling is unregulated in sensory neurons after chronic compression of the dorsal root ganglion. Proc Natl Acad Sci USA 2005; 102: 14092-7.PubMedCrossRef White FA, Sun J, Waters SM, et al. Excitatory monocyte chemoattractant protein-1 signalling is unregulated in sensory neurons after chronic compression of the dorsal root ganglion. Proc Natl Acad Sci USA 2005; 102: 14092-7.PubMedCrossRef
35.
Zurück zum Zitat Jin X, Gereau RW 4th. Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-alpha. J Neurosci 2006; 26: 246-55.PubMedCrossRef Jin X, Gereau RW 4th. Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-alpha. J Neurosci 2006; 26: 246-55.PubMedCrossRef
36.
Zurück zum Zitat Zhuang ZY, Kawasaki Y, Tan PH, Wen YR, Huang J, Ji RR. Role of the CXCR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine. Brain Behav Immun 2007; 21: 642-51.PubMedCentralPubMedCrossRef Zhuang ZY, Kawasaki Y, Tan PH, Wen YR, Huang J, Ji RR. Role of the CXCR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine. Brain Behav Immun 2007; 21: 642-51.PubMedCentralPubMedCrossRef
37.
Zurück zum Zitat Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 2007; 87: 659-797.PubMedCrossRef Burnstock G. Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 2007; 87: 659-797.PubMedCrossRef
38.
Zurück zum Zitat Ji R, Befort K, Brenner GJ, Woolf CJ. ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity. J Neursci 2002; 22: 478-85. Ji R, Befort K, Brenner GJ, Woolf CJ. ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity. J Neursci 2002; 22: 478-85.
39.
Zurück zum Zitat Kim SS, Bae JC, Kim JY, et al. Activation of p38 MAP kinase in the rat dorsal root ganglia and spinal cord following peripheral inflammation and nerve injury. Neuroreport 2002; 13: 2483-6.PubMedCrossRef Kim SS, Bae JC, Kim JY, et al. Activation of p38 MAP kinase in the rat dorsal root ganglia and spinal cord following peripheral inflammation and nerve injury. Neuroreport 2002; 13: 2483-6.PubMedCrossRef
40.
Zurück zum Zitat Piao ZG, Cho IH, Park CK, et al. Activation of glia and microglia p38 MAPK in medullary dorsal horn contributes to tactile hypersensitivity following trigeminal sensory nerve injury. Pain 2006; 121: 219-31.PubMedCrossRef Piao ZG, Cho IH, Park CK, et al. Activation of glia and microglia p38 MAPK in medullary dorsal horn contributes to tactile hypersensitivity following trigeminal sensory nerve injury. Pain 2006; 121: 219-31.PubMedCrossRef
41.
Zurück zum Zitat Svensson CI, Marsala M, Westerlund A, et al. Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced spinal pain processing. J Neurochem 2003; 86: 1534-44.PubMedCrossRef Svensson CI, Marsala M, Westerlund A, et al. Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammation-induced spinal pain processing. J Neurochem 2003; 86: 1534-44.PubMedCrossRef
42.
Zurück zum Zitat Khakh BS. Molecular physiology of P2X receptors and ATP signalling at synapses. Nat Rev Neurosci 2001; 2: 165-74.PubMedCrossRef Khakh BS. Molecular physiology of P2X receptors and ATP signalling at synapses. Nat Rev Neurosci 2001; 2: 165-74.PubMedCrossRef
43.
Zurück zum Zitat Pertovaara A. The noradrenergic pain regulation system: A potential target for pain therapy. Eur J Pharmacol 2013; 716: 2-7.PubMedCrossRef Pertovaara A. The noradrenergic pain regulation system: A potential target for pain therapy. Eur J Pharmacol 2013; 716: 2-7.PubMedCrossRef
44.
Zurück zum Zitat Woolf CJ, Salter MW. Neuronal Plasticity: Increasing the Gain in Pain. Science 2000; 288: 1765-9.PubMedCrossRef Woolf CJ, Salter MW. Neuronal Plasticity: Increasing the Gain in Pain. Science 2000; 288: 1765-9.PubMedCrossRef
45.
Zurück zum Zitat Woolf CJ, King AE. Dynmaic alterations in the cutaneous mechanoreceptive fields of dorsal horn neurons in the rat spinal cord. J Neurosci 1990; 10: 2717-26.PubMed Woolf CJ, King AE. Dynmaic alterations in the cutaneous mechanoreceptive fields of dorsal horn neurons in the rat spinal cord. J Neurosci 1990; 10: 2717-26.PubMed
46.
Zurück zum Zitat Simone DA, Sorkin LS, Oh U, et al. Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons. J Neurophysiol 1991; 66: 228-46.PubMed Simone DA, Sorkin LS, Oh U, et al. Neurogenic hyperalgesia: central neural correlates in responses of spinothalamic tract neurons. J Neurophysiol 1991; 66: 228-46.PubMed
47.
Zurück zum Zitat Guo W, Wei F, Zou S, et al. Group I metabotropic glutamate receptor NMDA receptors coupling and signalling cascade mediate spinal dorsal horn NMDA receptors 2B tyrosine phosphorylation associated with inflammatory hyperalgesia. J Neurosci 2004; 24: 9161-73.PubMedCrossRef Guo W, Wei F, Zou S, et al. Group I metabotropic glutamate receptor NMDA receptors coupling and signalling cascade mediate spinal dorsal horn NMDA receptors 2B tyrosine phosphorylation associated with inflammatory hyperalgesia. J Neurosci 2004; 24: 9161-73.PubMedCrossRef
48.
Zurück zum Zitat Chen L, Huang LY. Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 1992; 356: 521-3.PubMedCrossRef Chen L, Huang LY. Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 1992; 356: 521-3.PubMedCrossRef
49.
Zurück zum Zitat Qui S, Chen T, Koga K et al. An increase in synaptic NMDA receptors in the insular cortex contributes to neuropathic pain. Sci Signal 2013; 6: ra34. Qui S, Chen T, Koga K et al. An increase in synaptic NMDA receptors in the insular cortex contributes to neuropathic pain. Sci Signal 2013; 6: ra34.
50.
Zurück zum Zitat Afrah AW, Fiskå A, Gjerstad J, Gustafsson H, et al. Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons. Pain 2002; 96: 49-55.PubMedCrossRef Afrah AW, Fiskå A, Gjerstad J, Gustafsson H, et al. Spinal substance P release in vivo during the induction of long-term potentiation in dorsal horn neurons. Pain 2002; 96: 49-55.PubMedCrossRef
51.
Zurück zum Zitat Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA. Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci 2002; 22: 9086-98.PubMed Khasabov SG, Rogers SD, Ghilardi JR, Peters CM, Mantyh PW, Simone DA. Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci 2002; 22: 9086-98.PubMed
52.
Zurück zum Zitat Sun RQ, Lawand NB, Willis WD. The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of caspsaicin. Pain 2008; 104: 201-8.CrossRef Sun RQ, Lawand NB, Willis WD. The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of caspsaicin. Pain 2008; 104: 201-8.CrossRef
53.
Zurück zum Zitat Balkowiec A, Katz DM. Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected from ELISA in situ. J Neurosci 2000; 20: 7417-23.PubMed Balkowiec A, Katz DM. Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected from ELISA in situ. J Neurosci 2000; 20: 7417-23.PubMed
54.
Zurück zum Zitat Pitcher MH, Ribeiro-da-Silva A, Coderre TJ. Effects of inflammation on the ultrastructural localization of spinal dorsal horn group 1 metabotropic glutamate receptors. J Comp Neurol 2007; 505: 412-23.PubMedCrossRef Pitcher MH, Ribeiro-da-Silva A, Coderre TJ. Effects of inflammation on the ultrastructural localization of spinal dorsal horn group 1 metabotropic glutamate receptors. J Comp Neurol 2007; 505: 412-23.PubMedCrossRef
55.
Zurück zum Zitat Fang L, Wu J, Lin Q, Willis WD. Calcium-calmodulin-dependent protein kinase II contributes to spinal cord central sensitization. J Neurosci 2002; 22: 4196-204.PubMed Fang L, Wu J, Lin Q, Willis WD. Calcium-calmodulin-dependent protein kinase II contributes to spinal cord central sensitization. J Neurosci 2002; 22: 4196-204.PubMed
56.
Zurück zum Zitat Willis WD. Role of neurotransmitters in sensitization of pain responses. Ann NY Acad Sci 2001; 933: 142-56.PubMedCrossRef Willis WD. Role of neurotransmitters in sensitization of pain responses. Ann NY Acad Sci 2001; 933: 142-56.PubMedCrossRef
57.
Zurück zum Zitat Carvalho AL, Durate CB, Carvalho AP. Regulation of AMPA receptors by phosphorylation. Neurochem Res 2000; 25: 1245-55.PubMedCrossRef Carvalho AL, Durate CB, Carvalho AP. Regulation of AMPA receptors by phosphorylation. Neurochem Res 2000; 25: 1245-55.PubMedCrossRef
58.
Zurück zum Zitat Guo W, Zou S, Guan Y, et al. Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord during the development and maintenance of inflammatory hyperalgesia. J Neurosci 2002; 22: 6208-17.PubMed Guo W, Zou S, Guan Y, et al. Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord during the development and maintenance of inflammatory hyperalgesia. J Neurosci 2002; 22: 6208-17.PubMed
59.
Zurück zum Zitat Salter MW, Kalia LV. Src kinases: A hub for NMDA receptor regulation. Nature Rev Neurosci 2004; 5: 317-28.CrossRef Salter MW, Kalia LV. Src kinases: A hub for NMDA receptor regulation. Nature Rev Neurosci 2004; 5: 317-28.CrossRef
60.
Zurück zum Zitat Battaglia AA, Sehayek K, Grist J, McMahon S, Gavazzi I. EphB receptors and ephrin-B ligands regulate spinal sensory connectivity and modulate pain processing. Nat Neurosci 2003; 6: 339-40.PubMedCrossRef Battaglia AA, Sehayek K, Grist J, McMahon S, Gavazzi I. EphB receptors and ephrin-B ligands regulate spinal sensory connectivity and modulate pain processing. Nat Neurosci 2003; 6: 339-40.PubMedCrossRef
61.
Zurück zum Zitat Hu HJ, Alter BJ, Carrasquillo Y, Qiu CS, Gereau RW 4th. Metabotropic glutamate receptor 5 modulates nociceptive plasticity via extracellular signal-regulated kinase Kv4.2 signalling in spinal cord dorsal horn neurons. J Neurosci 2007; 27: 13181-91.PubMedCrossRef Hu HJ, Alter BJ, Carrasquillo Y, Qiu CS, Gereau RW 4th. Metabotropic glutamate receptor 5 modulates nociceptive plasticity via extracellular signal-regulated kinase Kv4.2 signalling in spinal cord dorsal horn neurons. J Neurosci 2007; 27: 13181-91.PubMedCrossRef
62.
Zurück zum Zitat Hu HJ, Carrasquillo Y, Karim F, et al. The kv4.2 potassium channel subunit is required for pain plasticity. Neuron 2006; 50: 89-100.PubMedCrossRef Hu HJ, Carrasquillo Y, Karim F, et al. The kv4.2 potassium channel subunit is required for pain plasticity. Neuron 2006; 50: 89-100.PubMedCrossRef
63.
Zurück zum Zitat Xing J, Kornhauser JM, Xia Z, Thiele EA, Greenberg ME. Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation. Mol Cell Biol 1998; 18: 1946-55.PubMedCentralPubMed Xing J, Kornhauser JM, Xia Z, Thiele EA, Greenberg ME. Nerve growth factor activates extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways to stimulate CREB serine 133 phosphorylation. Mol Cell Biol 1998; 18: 1946-55.PubMedCentralPubMed
64.
Zurück zum Zitat Costandil L, Aguilera R, Goich M, et al. Involvement of spinal cord BDNF in the generation and maintenance of chronic neuropathic pain in rats. Brain Res Bull 2011; 86: 454-9.CrossRef Costandil L, Aguilera R, Goich M, et al. Involvement of spinal cord BDNF in the generation and maintenance of chronic neuropathic pain in rats. Brain Res Bull 2011; 86: 454-9.CrossRef
65.
Zurück zum Zitat Obata K, Noguchi K. MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci 2004; 74: 2643-53.PubMedCrossRef Obata K, Noguchi K. MAPK activation in nociceptive neurons and pain hypersensitivity. Life Sci 2004; 74: 2643-53.PubMedCrossRef
66.
Zurück zum Zitat Costigan M, Befort K, Karchewski L, et al. Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 2002; 3: 16.PubMedCentralPubMedCrossRef Costigan M, Befort K, Karchewski L, et al. Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 2002; 3: 16.PubMedCentralPubMedCrossRef
67.
Zurück zum Zitat Xing J, Ginty DD, Greenberg ME. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 1996; 16: 959-63.CrossRef Xing J, Ginty DD, Greenberg ME. Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 1996; 16: 959-63.CrossRef
68.
Zurück zum Zitat Hunt SP, Pini A, Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 1987; 328: 632-4.PubMedCrossRef Hunt SP, Pini A, Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 1987; 328: 632-4.PubMedCrossRef
69.
Zurück zum Zitat Mannion RJ, Costigan M, Decosterd I, et al. Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity. Proc Natl Acad Sci USA 1999; 96: 9385-90.PubMedCrossRef Mannion RJ, Costigan M, Decosterd I, et al. Neurotrophins: peripherally and centrally acting modulators of tactile stimulus-induced inflammatory pain hypersensitivity. Proc Natl Acad Sci USA 1999; 96: 9385-90.PubMedCrossRef
70.
Zurück zum Zitat Neumann S, Doubell TP, Leslie T, Woolf CJ. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature 1996; 384: 360-4.PubMedCrossRef Neumann S, Doubell TP, Leslie T, Woolf CJ. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature 1996; 384: 360-4.PubMedCrossRef
71.
Zurück zum Zitat Noguchi K, Kawai Y, Fukuoka T, Senba E, Miki K. Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons. J Neurosci 1995; 15: 7633-43.PubMed Noguchi K, Kawai Y, Fukuoka T, Senba E, Miki K. Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons. J Neurosci 1995; 15: 7633-43.PubMed
72.
Zurück zum Zitat Tanga FY, Nutile-McMenemy N, DeLeo JA. The CNS role of Toll-like receptors 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci USA 2005; 102: 5856-61.PubMedCrossRef Tanga FY, Nutile-McMenemy N, DeLeo JA. The CNS role of Toll-like receptors 4 in innate neuroimmunity and painful neuropathy. Proc Natl Acad Sci USA 2005; 102: 5856-61.PubMedCrossRef
73.
Zurück zum Zitat Viviani B, Bartesaghi S, Gardoni F, et al. Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 2003; 24: 8692-700. Viviani B, Bartesaghi S, Gardoni F, et al. Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activation of the Src family of kinases. J Neurosci 2003; 24: 8692-700.
74.
Zurück zum Zitat Stellwagen D, Malenka RC. Synaptic scaling mediated by glial TNF-α. Nature 2006; 440: 1054-9.PubMedCrossRef Stellwagen D, Malenka RC. Synaptic scaling mediated by glial TNF-α. Nature 2006; 440: 1054-9.PubMedCrossRef
75.
Zurück zum Zitat Zhang RX, Li A, Liu B, et al. Il-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats. Pain 2008; 135: 232-9.PubMedCentralPubMedCrossRef Zhang RX, Li A, Liu B, et al. Il-1ra alleviates inflammatory hyperalgesia through preventing phosphorylation of NMDA receptor NR-1 subunit in rats. Pain 2008; 135: 232-9.PubMedCentralPubMedCrossRef
76.
Zurück zum Zitat Kitto KF, Haley JE, Wilcox GL. Involvement of nitric oxide in spinally mediated hyperalgesia in the mouse. Neurosci Lett 1992; 148: 1-5.PubMedCrossRef Kitto KF, Haley JE, Wilcox GL. Involvement of nitric oxide in spinally mediated hyperalgesia in the mouse. Neurosci Lett 1992; 148: 1-5.PubMedCrossRef
77.
Zurück zum Zitat Meller ST, Pechman PS, Gebhart GF, Maves TJ. Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat. Neurosci 1992; 50: 7-10.CrossRef Meller ST, Pechman PS, Gebhart GF, Maves TJ. Nitric oxide mediates the thermal hyperalgesia produced in a model of neuropathic pain in the rat. Neurosci 1992; 50: 7-10.CrossRef
78.
Zurück zum Zitat Nasu-Tada K, Koizumi S, Tsuda M, Kunifusa E, Inoue K. Possible involvement of increase in spinal fibronectin following peripheral nerve injury in upregulation of microglia P2X4, a key molecule for mechanical allodynia. Glia 2006; 53: 769-75.PubMedCrossRef Nasu-Tada K, Koizumi S, Tsuda M, Kunifusa E, Inoue K. Possible involvement of increase in spinal fibronectin following peripheral nerve injury in upregulation of microglia P2X4, a key molecule for mechanical allodynia. Glia 2006; 53: 769-75.PubMedCrossRef
79.
Zurück zum Zitat Nakagawa T, Wakamatsu K, Zhang N, et al. Intrathecal administration of ATP produces long-lasting allodynia in rats: differential mechanisms in the phase of the induction and maintenance. Neurosci 2007; 147: 445.CrossRef Nakagawa T, Wakamatsu K, Zhang N, et al. Intrathecal administration of ATP produces long-lasting allodynia in rats: differential mechanisms in the phase of the induction and maintenance. Neurosci 2007; 147: 445.CrossRef
80.
Zurück zum Zitat Nakagawa T, Wakamatsu K, Maeda S, Shirakawa H, Kaneko S. Differential contribution of spinal mitogen-activated protein kinases to the phase of long-lasting allodynia evoked by intrathecal administration of ATP in rats. Biol Pharm Bull 2008; 6: 1164-8.CrossRef Nakagawa T, Wakamatsu K, Maeda S, Shirakawa H, Kaneko S. Differential contribution of spinal mitogen-activated protein kinases to the phase of long-lasting allodynia evoked by intrathecal administration of ATP in rats. Biol Pharm Bull 2008; 6: 1164-8.CrossRef
81.
Zurück zum Zitat Trang T, Beggs S, Wan X, Salter MW. P2X4-receptor-mediated synthesis and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogen-activated protein kinase activation. J Neurosci 2009; 29: 3518-28.PubMedCentralPubMedCrossRef Trang T, Beggs S, Wan X, Salter MW. P2X4-receptor-mediated synthesis and release of brain-derived neurotrophic factor in microglia is dependent on calcium and p38-mitogen-activated protein kinase activation. J Neurosci 2009; 29: 3518-28.PubMedCentralPubMedCrossRef
82.
Zurück zum Zitat Coull JA, Beggs S, Boudreau D et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005; 438: 10-17-1021. Coull JA, Beggs S, Boudreau D et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005; 438: 10-17-1021.
83.
Zurück zum Zitat Coull JA, Boudreau D, Bachand K, et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003; 424: 938-42.PubMedCrossRef Coull JA, Boudreau D, Bachand K, et al. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003; 424: 938-42.PubMedCrossRef
84.
Zurück zum Zitat Gagnon M, Bergeron MJ, Lavertu G et al., Chloride extrusion enhancers as novel therapeutics for neurological diseases [published online ahead of print October 6 2013]. Nat Med. Doi:10.1038/nm.3356. Gagnon M, Bergeron MJ, Lavertu G et al., Chloride extrusion enhancers as novel therapeutics for neurological diseases [published online ahead of print October 6 2013]. Nat Med. Doi:10.​1038/​nm.​3356.
85.
Zurück zum Zitat White RJ. Wound infection-associated pain. J Wound Care 2009; 18: 245-9.PubMed White RJ. Wound infection-associated pain. J Wound Care 2009; 18: 245-9.PubMed
86.
Zurück zum Zitat Gardner SE, Frantz RA, Doebbeling BN. The validity of the clinical signs and symptoms used to identify localized chronic wound infection. Wound Repair Regen 2001; 3: 178-86.CrossRef Gardner SE, Frantz RA, Doebbeling BN. The validity of the clinical signs and symptoms used to identify localized chronic wound infection. Wound Repair Regen 2001; 3: 178-86.CrossRef
87.
Zurück zum Zitat Chiu IM, Heesters BA. Ghasemlou et al. Bacteria activate sensory neurons that modulate pain and inflammation. Nature 2013; 501: 52-7.PubMedCrossRef Chiu IM, Heesters BA. Ghasemlou et al. Bacteria activate sensory neurons that modulate pain and inflammation. Nature 2013; 501: 52-7.PubMedCrossRef
88.
Zurück zum Zitat Ruau D, Liu LY, Clark JD, Angst MS, Butte AJ. Sex differences in reported pain across 11,000 patients captured in electronic medical records. J Pain 2012; 13: 228-34.PubMedCentralPubMedCrossRef Ruau D, Liu LY, Clark JD, Angst MS, Butte AJ. Sex differences in reported pain across 11,000 patients captured in electronic medical records. J Pain 2012; 13: 228-34.PubMedCentralPubMedCrossRef
89.
Zurück zum Zitat Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci 2012; 13: 859-66.PubMedCrossRef Mogil JS. Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon. Nat Rev Neurosci 2012; 13: 859-66.PubMedCrossRef
90.
Zurück zum Zitat Kim SJ, Calejesan AA, Li P, Wei F, Zhuo M. Sex differences in late behavioural response to subcutaneous formalin injection in mice. Brain Res 1999; 829: 185-9.PubMedCrossRef Kim SJ, Calejesan AA, Li P, Wei F, Zhuo M. Sex differences in late behavioural response to subcutaneous formalin injection in mice. Brain Res 1999; 829: 185-9.PubMedCrossRef
91.
Zurück zum Zitat Gaumon I, Aresnault P, Marchand S. The role of sex hormones on formalin-induced nociceptive responses. Brain Res 2002; 958: 139-45.CrossRef Gaumon I, Aresnault P, Marchand S. The role of sex hormones on formalin-induced nociceptive responses. Brain Res 2002; 958: 139-45.CrossRef
92.
Zurück zum Zitat Perissin L, Facchin P, Porro CA. Tonic pain response in mice: effects of sex, season and time of day. Life Sci 2003; 72: 897-907.PubMedCrossRef Perissin L, Facchin P, Porro CA. Tonic pain response in mice: effects of sex, season and time of day. Life Sci 2003; 72: 897-907.PubMedCrossRef
93.
Zurück zum Zitat Aloisi AM, Ceccarelli I, Fiorenzani P, De Padova AM, Massafra C. Testosterone affects formalin-induced responses differently in male and female rats. Neurosci Lett 2004; 361: 262-4.PubMedCrossRef Aloisi AM, Ceccarelli I, Fiorenzani P, De Padova AM, Massafra C. Testosterone affects formalin-induced responses differently in male and female rats. Neurosci Lett 2004; 361: 262-4.PubMedCrossRef
94.
Zurück zum Zitat Vincler M, Maixner W, Vierck CJ, Light AR. Estrous cycle modulation of nociceptive behaviours elicited by electrical stimulation and formalin. Pharmacol Biochem Behav 2001; 69: 315-24.PubMedCrossRef Vincler M, Maixner W, Vierck CJ, Light AR. Estrous cycle modulation of nociceptive behaviours elicited by electrical stimulation and formalin. Pharmacol Biochem Behav 2001; 69: 315-24.PubMedCrossRef
95.
Zurück zum Zitat Gaumon I, Arsenault P, Marchand S. Specificity of female and male sex hormones on excitatory and inhibitory phase of formalin-induced nociceptive responses. Brain Res 2005; 1052: 105-11.CrossRef Gaumon I, Arsenault P, Marchand S. Specificity of female and male sex hormones on excitatory and inhibitory phase of formalin-induced nociceptive responses. Brain Res 2005; 1052: 105-11.CrossRef
96.
Zurück zum Zitat Bettoni I, Comelli F, Rossini C, et al. Glial TLR4 receptor as new target to treat neuropathic pain: efficacy of a new receptor antagonist in a model of peripheral nerve injury in mice. Glia 2008; 56: 1312-9.PubMedCrossRef Bettoni I, Comelli F, Rossini C, et al. Glial TLR4 receptor as new target to treat neuropathic pain: efficacy of a new receptor antagonist in a model of peripheral nerve injury in mice. Glia 2008; 56: 1312-9.PubMedCrossRef
97.
Zurück zum Zitat Sorge RE, LaCroix-Fralish MI, Tuttle AH, et al. Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J Neurosci 2011; 31: 15450-4.PubMedCentralPubMedCrossRef Sorge RE, LaCroix-Fralish MI, Tuttle AH, et al. Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J Neurosci 2011; 31: 15450-4.PubMedCentralPubMedCrossRef
Metadaten
Titel
The transition from acute to chronic pain: understanding how different biological systems interact
verfasst von
Katherine A. Mifflin, BSc
Bradley J. Kerr, PhD
Publikationsdatum
01.02.2014
Verlag
Springer US
Erschienen in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Ausgabe 2/2014
Print ISSN: 0832-610X
Elektronische ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-013-0087-4

Weitere Artikel der Ausgabe 2/2014

Canadian Journal of Anesthesia/Journal canadien d'anesthésie 2/2014 Zur Ausgabe

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

Delir bei kritisch Kranken – Antipsychotika versus Placebo

16.05.2024 Delir Nachrichten

Um die Langzeitfolgen eines Delirs bei kritisch Kranken zu mildern, wird vielerorts auf eine Akuttherapie mit Antipsychotika gesetzt. Eine US-amerikanische Forschungsgruppe äußert jetzt erhebliche Vorbehalte gegen dieses Vorgehen. Denn es gibt neue Daten zum Langzeiteffekt von Haloperidol bzw. Ziprasidon versus Placebo.

Eingreifen von Umstehenden rettet vor Erstickungstod

15.05.2024 Fremdkörperaspiration Nachrichten

Wer sich an einem Essensrest verschluckt und um Luft ringt, benötigt vor allem rasche Hilfe. Dass Umstehende nur in jedem zweiten Erstickungsnotfall bereit waren, diese zu leisten, ist das ernüchternde Ergebnis einer Beobachtungsstudie aus Japan. Doch es gibt auch eine gute Nachricht.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.