Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

References

• Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152:S2–15.
   PubMed Web of Science ®Google Scholar
• Merskey H, NBatITFo T. Part III: pain terms, a current list with definitions and notes on usage. In: Merskey H, NBatITFo T, editor. Classification of chronic pain. 2nd ed. Seattle, USA: IASP Press; 1994. p. 209–214.
   Google Scholar
• Rojewska E, Popiolek-Barczyk K, Jurga AM, et al. Involvement of pro- and antinociceptive factors in minocycline analgesia in rat neuropathic pain model. J Neuroimmunol. 2014;277:57–66.
   PubMed Web of Science ®Google Scholar
• Van Oosterwijck J, Nijs J, Meeus M, et al. Evidence for central sensitization in chronic whiplash: a systematic literature review. Eur J Pain. 2013;17:299–312.
   PubMed Web of Science ®Google Scholar
• Roussel NA, Nijs J, Meeus M, et al. Central sensitization and altered central pain processing in chronic low back pain: fact or myth? Clin J Pain. 2013;29:625–638.
   PubMed Web of Science ®Google Scholar
• Lluch Girbes E, Nijs J, Torres-Cueco R, et al. Pain treatment for patients with osteoarthritis and central sensitization. Phys Ther. 2013;93:842–851.
   PubMed Web of Science ®Google Scholar
• Perrotta A, Serrao M, Sandrini G, et al. Sensitisation of spinal cord pain processing in medication overuse headache involves supraspinal pain control. Cephalalgia. 2010;30:272–284.
   PubMed Web of Science ®Google Scholar
• Caro-Moran E, Diaz-Rodriguez L, Cantarero-Villanueva I, et al. Nerve pressure pain hypersensitivity and upper limb mechanosensitivity in breast cancer survivors: a case-control study. Pain Med. 2014;15:1715–1723.
   PubMed Web of Science ®Google Scholar
• Price DD, Staud R, Robinson ME, et al. Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients. Pain. 2002;99:49–59.
   PubMed Web of Science ®Google Scholar
• Sanchis MN, Lluch E, Nijs J, et al. The role of central sensitization in shoulder pain: a systematic literature review. Seminars in arthritis and rheumatism. 2015;44:710–716.
   Google Scholar
• Nijs J, Meeus M, Van Oosterwijck J, et al. In the mind or in the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome. Eur J Clin Invest. 2012;42:203–212.
   PubMed Web of Science ®Google Scholar
• Meeus M, Vervisch S, De Clerck LS, et al. Central sensitization in patients with rheumatoid arthritis: a systematic literature review. Semin Arthritis Rheum. 2012;41:556–567.
   PubMed Web of Science ®Google Scholar
• Raphael KG, Janal MN, Anathan S, et al. Temporal summation of heat pain in temporomandibular disorder patients. J Orofac Pain. 2009;23:54–64.
   PubMedGoogle Scholar
• Van Wilgen CP, Konopka KH, Keizer D, et al. Do patients with chronic patellar tendinopathy have an altered somatosensory profile? - A Quantitative Sensory Testing (QST) study. Scand J Med Sci Sports. 2013 Mar;23(2):149–155. doi: 10.1111/j.1600-0838.2011.01375.x.
   PubMed Web of Science ®Google Scholar
• Cornelison LE, Hawkins JL, Durham PL. Elevated levels of calcitonin gene-related peptide in upper spinal cord promotes sensitization of primary trigeminal nociceptive neurons. Neuroscience. 2016;339:491–501.
   PubMed Web of Science ®Google Scholar
• Coombes BK, Bisset L, Vicenzino B. Thermal hyperalgesia distinguishes those with severe pain and disability in unilateral lateral epicondylalgia. Clin J Pain. 2012;28:595–601.
   PubMed Web of Science ®Google Scholar
• Fernandez-Carnero J, Fernandez-de-Las-Penas C, De La Llave-Rincon AI, et al. Widespread mechanical pain hypersensitivity as sign of central sensitization in unilateral epicondylalgia: a blinded, controlled study. Clin J Pain. 2009;25:555–561.
   PubMed Web of Science ®Google Scholar
• Nijs J, Van Houdenhove B, Oostendorp RA. Recognition of central sensitization in patients with musculoskeletal pain: application of pain neurophysiology in manual therapy practice. Man Ther. 2010;15:135–141.
   PubMed Web of Science ®Google Scholar
• Baranauskas G, Nistri A. Sensitization of pain pathways in the spinal cord: cellular mechanisms. Prog Neurobiol. 1998;54:349–365.
   PubMed Web of Science ®Google Scholar
• Staud R, Craggs JG, Perlstein WM, et al. Brain activity associated with slow temporal summation of C-fiber evoked pain in fibromyalgia patients and healthy controls. Eur J Pain. 2008;12:1078–1089.
   PubMed Web of Science ®Google Scholar
• Seifert F, Maihofner C. Central mechanisms of experimental and chronic neuropathic pain: findings from functional imaging studies. Cell Mol Life Sci. 2009;66:375–390.
   PubMed Web of Science ®Google Scholar
• Becerra L, Veggeberg R, Prescot A, et al. A ‘complex’ of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients. NeuroImage Clin. 2016;11:588–594.
   PubMed Web of Science ®Google Scholar
• Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol. 2010;23:611–615.
   PubMed Web of Science ®Google Scholar
• Silva M, Costa-Pereira JT, Martins D, et al. Pain modulation from the brain during diabetic neuropathy: uncovering the role of the rostroventromedial medulla. Neurobiol Dis. 2016;96:346–356.
   PubMed Web of Science ®Google Scholar
• Ma QP, Woolf CJ. Noxious stimuli induce an N-methyl-D-aspartate receptor-dependent hypersensitivity of the flexion withdrawal reflex to touch: implications for the treatment of mechanical allodynia. Pain. 1995;61:383–390.
   PubMed Web of Science ®Google Scholar
• Neumann S, Doubell TP, Leslie T, et al. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons. Nature. 1996;384:360–364.
   PubMed Web of Science ®Google Scholar
• Nijs J, Torres-Cueco R, Van Wilgen CP, et al. Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain. Pain Physician. 2014;17:447–457.
   PubMed Web of Science ®Google Scholar
• Neblett R, Cohen H, Choi Y, et al. The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. J Pain. 2013;14:438–445.
   PubMed Web of Science ®Google Scholar
• Van Houdenhove B, Egle UT. Fibromyalgia: a stress disorder? Piecing the biopsychosocial puzzle together. Psychother Psychosom. 2004;73:267–275.
   PubMed Web of Science ®Google Scholar
• Austin PJ, Moalem-Taylor G. The neuro-immune balance in neuropathic pain: involvement of inflammatory immune cells, immune-like glial cells and cytokines. J Neuroimmunol. 2010;229:26–50.
   PubMed Web of Science ®Google Scholar
• Delpech JC, Madore C, Nadjar A, et al. Microglia in neuronal plasticity: influence of stress. Neuropharmacology. 2015;96:19–28.
   PubMed Web of Science ®Google Scholar
• Fields RD, Araque A, Johansen-Berg H, et al. Glial biology in learning and cognition. Neuroscientist. 2014;20:426–431.
   PubMed Web of Science ®Google Scholar
• Clarke LE, Barres BA. Emerging roles of astrocytes in neural circuit development. Nat Reviews Neurosci. 2013;14:311–321.
   PubMed Web of Science ®Google Scholar
• Agostini S, Eutamene H, Cartier C, et al. Evidence of central and peripheral sensitization in a rat model of narcotic bowel-like syndrome. Gastroenterology. 2010;139:553-63, 63 e1-5.
   PubMed Web of Science ®Google Scholar
• Bjurstrom MF, Giron SE, Griffis CA. Cerebrospinal fluid cytokines and neurotrophic factors in human chronic pain populations: a comprehensive review. Pain Pract. 2016;16:183–203.
   PubMed Web of Science ®Google Scholar
• Loggia ML, Chonde DB, Akeju O, et al. Evidence for brain glial activation in chronic pain patients. Brain: J Neurol. 2015;138:604–615.
   Web of Science ®Google Scholar
• Sorge RE, Mapplebeck JC, Rosen S, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci. 2015;18:1081–1083.
   PubMed Web of Science ®Google Scholar
• Wisor JP, Schmidt MA, Clegern WC. Cerebral microglia mediate sleep/wake and neuroinflammatory effects of methamphetamine. Brain Behav Immun. 2011;25:767–776.
   PubMed Web of Science ®Google Scholar
• Reader BF, Jarrett BL, McKim DB, et al. Peripheral and central effects of repeated social defeat stress: monocyte trafficking, microglial activation, and anxiety. Neuroscience. 2015;289:429–442.
   PubMed Web of Science ®Google Scholar
• Wohleb ES, McKim DB, Sheridan JF, et al. Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior. Front Neurosci. 2014;8:447.
   PubMed Web of Science ®Google Scholar
• Gritsch S, Lu J, Thilemann S, et al. Oligodendrocyte ablation triggers central pain independently of innate or adaptive immune responses in mice. Nat Commun. 2014;5:5472.
   PubMed Web of Science ®Google Scholar
• Spielman LJ, Little JP, Klegeris A. Physical activity and exercise attenuate neuroinflammation in neurological diseases. Brain Res Bull. 2016;125:19–29.
   PubMed Web of Science ®Google Scholar
• Li W, Ma L, Yang G, et al. REM sleep selectively prunes and maintains new synapses in development and learning. Nat Neurosci. 2017;20:427–437.
   PubMed Web of Science ®Google Scholar
• Fontainhas AM, Wang M, Liang KJ, et al. Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission. PloS One. 2011;6:e15973.
   PubMed Web of Science ®Google Scholar
• Svensson M, Lexell J, Deierborg T. Effects of physical exercise on neuroinflammation, neuroplasticity, neurodegeneration, and behavior: what we can learn from animal models in clinical settings. Neurorehabil Neural Repair. 2015;29:577–589.
   PubMed Web of Science ®Google Scholar
• Taves S, Berta T, Liu DL, et al. Spinal inhibition of p38 MAP kinase reduces inflammatory and neuropathic pain in male but not female mice: sex-dependent microglial signaling in the spinal cord. Brain Behav Immun. 2016;55:70–81.
   PubMed Web of Science ®Google Scholar
• Kiyomoto M, Shinoda M, Honda K, et al. p38 phosphorylation in medullary microglia mediates ectopic orofacial inflammatory pain in rats. Mol Pain. 2015;11:48.
   PubMed Web of Science ®Google Scholar
• Crotti A, Ransohoff RM. Microglial physiology and pathophysiology: insights from genome-wide transcriptional profiling. Immunity. 2016;44:505–515.
   PubMed Web of Science ®Google Scholar
• Wang ML, Li WB. Cognitive impairment after traumatic brain injury: the role of MRI and possible pathological basis. J Neurol Sci. 2016;370:244–250.
   PubMed Web of Science ®Google Scholar
• Liu C, Li CP, Wang JJ, et al. RNCR3 knockdown inhibits diabetes mellitus-induced retinal reactive gliosis. Biochem Biophys Res Commun. 2016;479:198–203.
   PubMed Web of Science ®Google Scholar
• Campbell JG, Miller DC, Cundiff DD, et al. Neural stem/progenitor cells react to non-glial cns neoplasms. SpringerPlus. 2015;4:53.
   PubMed Web of Science ®Google Scholar
• Ji RR, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy? Pain. 2013;154(Suppl 1):S10–28.
   PubMed Web of Science ®Google Scholar
• Guida F, Luongo L, Aviello G, et al. Salvinorin A reduces mechanical allodynia and spinal neuronal hyperexcitability induced by peripheral formalin injection. Mol Pain. 2012;8:60.
   PubMed Web of Science ®Google Scholar
• Luongo L, Guida F, Boccella S, et al. Palmitoylethanolamide reduces formalin-induced neuropathic-like behaviour through spinal glial/microglial phenotypical changes in mice. CNS Neurol Disord Drug Targets. 2013;12:45–54.
   PubMed Web of Science ®Google Scholar
• Clark AK, Staniland AA, Malcangio M. Fractalkine/CX3CR1 signalling in chronic pain and inflammation. Curr Pharm Biotechnol. 2011;12:1707–1714.
   PubMed Web of Science ®Google Scholar
• Smith PA. BDNF: no gain without pain?. Neuroscience. 2014 Dec 26;283:107–123. doi: 10.1016/j.neuroscience.2014.05.044.
   Web of Science ®Google Scholar
• Ferrini F, De Koninck Y. Microglia control neuronal network excitability via BDNF signalling. Neural Plast. 2013;2013:429815.
   PubMed Web of Science ®Google Scholar
• Nijs J, Meeus M, Versijpt J, et al. Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target? Expert Opin Ther Targets. 2015;19:565–576.
   PubMed Web of Science ®Google Scholar
• Gao YJ, Ji RR. Activation of JNK pathway in persistent pain. Neurosci Lett. 2008;437:180–183.
   PubMed Web of Science ®Google Scholar
• Ji RR, Kohno T, Moore KA, et al. Central sensitization and LTP: do pain and memory share similar mechanisms? Trends Neurosci. 2003;26:696–705.
   PubMed Web of Science ®Google Scholar
• Zhou LJ, Yang T, Wei X, et al. Brain-derived neurotrophic factor contributes to spinal long-term potentiation and mechanical hypersensitivity by activation of spinal microglia in rat. Brain Behav Immun. 2011;25:322–334.
   PubMed Web of Science ®Google Scholar
• Zhuo M. A synaptic model for pain: long-term potentiation in the anterior cingulate cortex. Mol Cells. 2007;23:259–271.
   PubMed Web of Science ®Google Scholar
• Apkarian AV, Mutso AA, Centeno MV, et al. Role of adult hippocampal neurogenesis in persistent pain. Pain. 2016;157:418–428.
   PubMed Web of Science ®Google Scholar
• Nijs J, Lluch Girbes E, Lundberg M, et al. Exercise therapy for chronic musculoskeletal pain: innovation by altering pain memories. Man Ther. 2015;20:216–220.
   PubMed Web of Science ®Google Scholar
• Ji RR, Berta T, Nedergaard M. Glia and pain: is chronic pain a gliopathy? Pain. 2013;154(Suppl):1.
   PubMed Web of Science ®Google Scholar
• Ji RR, Kawasaki Y, Zhuang ZY, et al. Possible role of spinal astrocytes in maintaining chronic pain sensitization: review of current evidence with focus on bFGF/JNK pathway. Neuron Glia Biol. 2006;2:259–269.
   PubMedGoogle Scholar
• Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med. 2010;16:1267–1276.
   PubMed Web of Science ®Google Scholar
• Guo W, Wang H, Watanabe M, et al. Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. J Neurosci. 2007;27:6006–6018.
   PubMed Web of Science ®Google Scholar
• Okada-Ogawa A, Suzuki I, Sessle BJ, et al. Astroglia in medullary dorsal horn (trigeminal spinal subnucleus caudalis) are involved in trigeminal neuropathic pain mechanisms. J Neurosci. 2009;29:11161–11171.
   PubMed Web of Science ®Google Scholar
• Meller ST, Dykstra C, Grzybycki D, et al. The possible role of glia in nociceptive processing and hyperalgesia in the spinal cord of the rat. Neuropharmacology. 1994;33:1471–1478.
   PubMed Web of Science ®Google Scholar
• Chen G, Park CK, Xie RG, et al. Connexin-43 induces chemokine release from spinal cord astrocytes to maintain late-phase neuropathic pain in mice. Brain. 2014;137:2193–2209.
   PubMed Web of Science ®Google Scholar
• Luongo L, Guida F, Imperatore R, et al. The A1 adenosine receptor as a new player in microglia physiology. Glia. 2014;62:122–132.
   PubMed Web of Science ®Google Scholar
• Liu S, Liu YP, Yue DM, et al. Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain. Eur J Pain. 2014 Mar;18(3):326–337. doi: 10.1002/j.1532-2149.2013.00372.x..
   Web of Science ®Google Scholar
• Grant AD, Cottrell GS, Amadesi S, et al. Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J Physiol. 2007;578:715–733.
   PubMed Web of Science ®Google Scholar
• Amadesi S, Nie J, Vergnolle N, et al. Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia. J Neuroscience: Official Journal Soc Neurosci. 2004;24:4300–4312.
   PubMed Web of Science ®Google Scholar
• Rothmeier AS, Ruf W. Protease-activated receptor 2 signaling in inflammation. Semin Immunopathol. 2012;34:133–149.
   PubMed Web of Science ®Google Scholar
• Bao Y, Hou W, Liu R, et al. PAR2-mediated upregulation of BDNF contributes to central sensitization in bone cancer pain. Mol Pain. 2014;10:28.
   PubMed Web of Science ®Google Scholar
• Watkins LR, Martin D, Ulrich P, et al. Evidence for the involvement of spinal cord glia in subcutaneous formalin induced hyperalgesia in the rat. Pain. 1997;71:225–235.
   PubMed Web of Science ®Google Scholar
• Banati RB, Cagnin A, Brooks DJ, et al. Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury. Neuroreport. 2001;12:3439–3442.
   PubMed Web of Science ®Google Scholar
• Schouten M, Aschrafi A, Bielefeld P, et al. microRNAs and the regulation of neuronal plasticity under stress conditions. Neuroscience. 2013;241:188–205.
   PubMed Web of Science ®Google Scholar
• Rosenbloom BN, Katz J, Chin KY, et al. Predicting pain outcomes after traumatic musculoskeletal injury. Pain. 2016;157:1733–1743.
   PubMed Web of Science ®Google Scholar
• Tesarz J, Eich W, Treede RD, et al. Altered pressure pain thresholds and increased wind-up in adult patients with chronic back pain with a history of childhood maltreatment: a quantitative sensory testing study. Pain. 2016;157:1799–1809.
   PubMed Web of Science ®Google Scholar
• Anderson G, Maes M. Schizophrenia: linking prenatal infection to cytokines, the tryptophan catabolite (TRYCAT) pathway, NMDA receptor hypofunction, neurodevelopment and neuroprogression. Prog Neuropsychopharmacol Biol Psychiatry. 2013;42:5–19.
   PubMed Web of Science ®Google Scholar
• Radley J, Morilak D, Viau V, et al. Chronic stress and brain plasticity: mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders. Neurosci Biobehav Rev. 2015;58:79–91.
   PubMed Web of Science ®Google Scholar
• Vyas A, Mitra R, Shankaranarayana Rao BS, et al. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neuroscience: Official Journal Soc Neurosci. 2002;22:6810–6818.
   PubMed Web of Science ®Google Scholar
• Zandieh S, Bernt R, Knoll P, et al. Analysis of the metabolic and structural brain changes in patients with torture-related post-traumatic stress disorder (TR-PTSD) Using (1, 8)F-FDG PET and MRI. Medicine. 2016;95:e3387.
   PubMed Web of Science ®Google Scholar
• Gracely RH, Geisser ME, Giesecke T, et al. Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain: J Neurol. 2004;127:835–843.
   Web of Science ®Google Scholar
• Li Z, Wang J, Chen L, et al. Basolateral amygdala lesion inhibits the development of pain chronicity in neuropathic pain rats. PloS One. 2013 Aug 5;8(8):e70921. doi: 10.1371/journal.pone.0070921. Print 2013.
   Web of Science ®Google Scholar
• Lutz J, Jager L, De Quervain D, et al. White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study. Arthritis Rheum. 2008;58:3960–3969.
   PubMed Web of Science ®Google Scholar
• McEwen BS, Eiland L, Hunter RG, et al. Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology. 2012;62:3–12.
   PubMed Web of Science ®Google Scholar
• Leuner B, Shors TJ. Stress, anxiety, and dendritic spines: what are the connections? Neuroscience. 2013;251:108–119.
   PubMed Web of Science ®Google Scholar
• Jungquist CR, O’Brien C, Matteson-Rusby S, et al. The efficacy of cognitive-behavioral therapy for insomnia in patients with chronic pain. Sleep Med. 2010;11:302–309.
   PubMed Web of Science ®Google Scholar
• Pigeon WR, Moynihan J, Matteson-Rusby S, et al. Comparative effectiveness of CBT interventions for co-morbid chronic pain & insomnia: a pilot study. Behav Res Ther. 2012;50:685–689.
   PubMed Web of Science ®Google Scholar
• Becker N, Bondegaard Thomsen A, Olsen AK, et al. Pain epidemiology and health related quality of life in chronic non-malignant pain patients referred to a Danish multidisciplinary pain center. Pain. 1997;73:393–400.
   PubMed Web of Science ®Google Scholar
• McCracken LM, Iverson GL. Disrupted sleep patterns and daily functioning in patients with chronic pain. Pain Res & Manage. 2002;7:75–79.
   PubMedGoogle Scholar
• Tang NK, Wright KJ, Salkovskis PM. Prevalence and correlates of clinical insomnia co-occurring with chronic back pain. J Sleep Res. 2007;16:85–95.
   PubMed Web of Science ®Google Scholar
• Daly-Eichenhardt A, Scott W, Howard-Jones M, et al. Changes in sleep problems and psychological flexibility following interdisciplinary acceptance and commitment therapy for chronic pain: an observational cohort study. Front Psychol. 2016;7:1326.
   PubMed Web of Science ®Google Scholar
• Kim EJ, Dimsdale JE. The effect of psychosocial stress on sleep: a review of polysomnographic evidence. Behav Sleep Med. 2007;5:256–278.
   PubMedGoogle Scholar
• Onen SH, Alloui A, Gross A, et al. The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects. J Sleep Res. 2001;10:35–42.
   PubMed Web of Science ®Google Scholar
• Schuh-Hofer S, Wodarski R, Pfau DB, et al. One night of total sleep deprivation promotes a state of generalized hyperalgesia: a surrogate pain model to study the relationship of insomnia and pain. Pain. 2013;154:1613–1621.
   PubMed Web of Science ®Google Scholar
• Lopez-Canul M, Palazzo E, Dominguez-Lopez S, et al. Selective melatonin MT2 receptor ligands relieve neuropathic pain through modulation of brainstem descending antinociceptive pathways. Pain. 2015;156:305–317.
   PubMed Web of Science ®Google Scholar
• Lopez-Canul M, Comai S, Dominguez-Lopez S, et al. Antinociceptive properties of selective MT(2) melatonin receptor partial agonists. Eur J Pharmacol. 2015;764:424–432.
   PubMed Web of Science ®Google Scholar
• Mullington JM, Simpson NS, Meier-Ewert HK, et al. Sleep loss and inflammation. Best Pract Res Clin Endocrinol Metab. 2010;24:775–784.
   PubMed Web of Science ®Google Scholar
• Haack M, Lee E, Cohen DA, et al. Activation of the prostaglandin system in response to sleep loss in healthy humans: potential mediator of increased spontaneous pain. Pain. 2009;145:136–141.
   PubMed Web of Science ®Google Scholar
• Haack M, Sanchez E, Mullington JM. Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers. Sleep. 2007;30:1145–1152.
   PubMed Web of Science ®Google Scholar
• Pollmacher T, Haack M, Schuld A, et al. Low levels of circulating inflammatory cytokines–do they affect human brain functions? Brain Behav Immun. 2002;16:525–532.
   PubMed Web of Science ®Google Scholar
• Wodarski R, Schuh-Hofer S, Yurek DA, et al. Development and pharmacological characterization of a model of sleep disruption-induced hypersensitivity in the rat. Eur J Pain. 2015;19:554–566.
   PubMed Web of Science ®Google Scholar
• Kiernan EA, Smith SM, Mitchell GS, et al. Mechanisms of microglial activation in models of inflammation and hypoxia: implications for chronic intermittent hypoxia. J Physiol. 2016;594:1563–1577.
   PubMed Web of Science ®Google Scholar
• Hou Y, Xie G, Liu X, et al. Minocycline protects against lipopolysaccharide-induced cognitive impairment in mice. Psychopharmacology. 2016;233:905–916.
   PubMed Web of Science ®Google Scholar
• Jin WJ, Feng SW, Feng Z, et al. Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation. Neuroreport. 2014;25:1–6.
   PubMed Web of Science ®Google Scholar
• Sun JS, Yang YJ, Zhang YZ, et al. Minocycline attenuates pain by inhibiting spinal microglia activation in diabetic rats. Mol Med Rep. 2015;12:2677–2682.
   PubMed Web of Science ®Google Scholar
• Vanelderen P, Van Zundert J, Kozicz T, et al. Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo-controlled, double-blind clinical trial with amitriptyline as a comparator. Anesthesiology. 2015;122:399–406.
   PubMed Web of Science ®Google Scholar
• Wohleb ES, Hanke ML, Corona AW, et al. beta-Adrenergic receptor antagonism prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat. J Neuroscience: Official Journal Soc Neurosci. 2011;31:6277–6288.
   PubMed Web of Science ®Google Scholar
• Shibakawa YS, Sasaki Y, Goshima Y, et al. Effects of ketamine and propofol on inflammatory responses of primary glial cell cultures stimulated with lipopolysaccharide. Br J Anaesth. 2005;95:803–810.
   PubMed Web of Science ®Google Scholar
• Gomes FV, Llorente R, Del Bel EA, et al. Decreased glial reactivity could be involved in the antipsychotic-like effect of cannabidiol. Schizophr Res. 2015;164:155–163.
   PubMed Web of Science ®Google Scholar
• Landry RP, Jacobs VL, Romero-Sandoval EA, et al. Propentofylline, a CNS glial modulator does not decrease pain in post-herpetic neuralgia patients: in vitro evidence for differential responses in human and rodent microglia and macrophages. Exp Neurol. 2012;234:340–350.
   PubMed Web of Science ®Google Scholar
• Almeida C, DeMaman A, Kusuda R, et al. Exercise therapy normalizes BDNF upregulation and glial hyperactivity in a mouse model of neuropathic pain. Pain. 2015;156:504–513.
   PubMed Web of Science ®Google Scholar
• Commentary on Landry; Watkins LR, Hutchinson MR, Johnson KW, et al. “Propentofylline, a CNS glial modulator, does not decrease pain in post-herpetic neuralgia patients: in vitro evidence for differential responses in human and rodent microglia and macrophages”. Exp Neurol. 2012;234:351–353.
   PubMed Web of Science ®Google Scholar
• Zhuang ZY, Gerner P, Woolf CJ, et al. ERK is sequentially activated in neurons, microglia, and astrocytes by spinal nerve ligation and contributes to mechanical allodynia in this neuropathic pain model. Pain. 2005;114:149–159.
   PubMed Web of Science ®Google Scholar
• Wilhelmsson U, Bushong EA, Price DL, et al. Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proceedings of the National Academy of Sciences of the United States of America. 2006;103:17513–17518.
   Google Scholar
• Sorge RE, LaCroix-Fralish ML, Tuttle AH, et al. Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J Neuroscience: Official Journal Soc Neurosci. 2011;31:15450–15454.
   PubMed Web of Science ®Google Scholar
• Rosen S, Ham B, Mogil JS. Sex differences in neuroimmunity and pain. J Neurosci Res. 2017;95:500–508.
   PubMed Web of Science ®Google Scholar
• Saur L, Baptista PP, De Senna PN, et al. Physical exercise increases GFAP expression and induces morphological changes in hippocampal astrocytes. Brain Struct Funct. 2014;219:293–302.
   PubMed Web of Science ®Google Scholar
• Coelho FG, Gobbi S, Andreatto CA, et al. Physical exercise modulates peripheral levels of brain-derived neurotrophic factor (BDNF): a systematic review of experimental studies in the elderly. Arch Gerontol Geriatr. 2013;56:10–15.
   PubMed Web of Science ®Google Scholar
• Knaepen K, Goekint M, Heyman EM, et al. Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sports Med. 2010;40:765–801.
   PubMed Web of Science ®Google Scholar
• Rinaldi B, Guida F, Furiano A, et al. Effect of prolonged moderate exercise on the changes of nonneuronal cells in early myocardial infarction. Neural Plast. 2015;2015:265967.
   PubMed Web of Science ®Google Scholar
• Henriksen M, Klokker L, Graven-Nielsen T, et al. Association of exercise therapy and reduction of pain sensitivity in patients with knee osteoarthritis: a randomized controlled trial. Arthritis Care Res (Hoboken). 2014;66:1836–1843.
   PubMed Web of Science ®Google Scholar
• Andersen LL, Andersen CH, Sundstrup E, et al. Central adaptation of pain perception in response to rehabilitation of musculoskeletal pain: randomized controlled trial. Pain Physician. 2012;15:385–394.
   PubMed Web of Science ®Google Scholar
• Chang CK, Chou W, Lin HJ, et al. Exercise preconditioning protects against spinal cord injury in rats by upregulating neuronal and astroglial heat shock protein 72. Int J Mol Sci. 2014;15:19018–19036.
   PubMed Web of Science ®Google Scholar
• Sheppard PW, Sun X, Khammash M, et al. Overexpression of heat shock protein 72 attenuates NF-kappaB activation using a combination of regulatory mechanisms in microglia. PLoS Comput Biol. 2014;10:e1003471.
   PubMed Web of Science ®Google Scholar