Abstract
Pain is one of the most challenging symptoms for patients with rheumatoid arthritis (RA). RA-related pain is frequently considered to be solely a consequence of inflammation in the joints; however, recent studies show that multiple mechanisms are involved. Indeed, RA pain may start even before the disease manifests, and frequently does not correlate with the degree of inflammation or pharmacological management. In this aspect, animal studies have the potential to provide new insights into the pathology that initiate and maintain pain in RA. The focus of this review is to describe the most commonly used animal models for studies of RA pathology, which have also been utilized in pain research, and to summarize findings providing potential clues to the mechanisms involved in the regulation of RA-induced pain.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1 . Seven year changes in health status and priorities for improvement of health in patients with rheumatoid arthritis. Ann. Rheum. Dis. 64(2), 191–195 (2005).
- 2 . Changes in priorities for improvement in patients with rheumatoid arthritis during 1 year of anti-tumour necrosis factor treatment. Ann. Rheum. Dis. 66(11), 1485–1490 (2007).
- 3 Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 48(10), 2741–2749 (2003).
- 4 Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 50(2), 380–386 (2004).
- 5 Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study. Ann. Rheum. Dis. 69(3), 490–494 (2010).
- 6 Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis. Arthritis Rheum. 63(11), 3226–3233 (2011).
- 7 . Description of stable pain in rheumatoid arthritis: a 6 year study. J. Rheumatol. 30(8), 1733–1738 (2003).
- 8 . Neuropathic-like pain features and cross-sectional associations in rheumatoid arthritis. Arthritis Res. Ther. 17(1), 237 (2015).
- 9 . Is the disease course of rheumatoid arthritis becoming milder? Time trends since 1985 in an inception cohort of early rheumatoid arthritis. Arthritis Rheum. 52(9), 2616–2624 (2005).
- 10 Subgrouping of patients with rheumatoid arthritis based on pain, fatigue, inflammation, and psychosocial factors. Arthritis Rheumatol. 66(8), 2006–2014 (2014).
- 11 Patient perceptions concerning pain management in the treatment of rheumatoid arthritis. J. Int. Med. Res. 38(4), 1213–1224 (2010).
- 12 Pain persists in DAS28 rheumatoid arthritis remission but not in ACR/EULAR remission: a longitudinal observational study. Arthritis Res. Ther. 13(3), R83 (2011). • This study is pointing the importance of pain problem in rheumatoid arthritis (RA) patients and highlighting that the inflammation is not the only component in RA pain.
- 13 . Meta-analysis of tight control strategies in rheumatoid arthritis: protocolized treatment has additional value with respect to the clinical outcome. Rheumatology (Oxford) 49(11), 2154–2164 (2010).
- 14 . Pain management in patients with rheumatoid arthritis. Nurse Pract. 40(5), 38–45 (2015).
- 15 . The value of animal models in predicting genetic susceptibility to complex diseases such as rheumatoid arthritis. Arthritis Res. Ther. 11(3), 226 (2009).
- 16 . Advances in research on animal models of rheumatoid arthritis. Clin. Rheumatol. 32(2), 161–165 (2013). • This review paper is showing recent findings in different animal models of RA.
- 17 Collagen-induced arthritis as a model of hyperalgesia: functional and cellular analysis of the analgesic actions of tumor necrosis factor blockade. Arthritis Rheum. 56(12), 4015–4023 (2007). •• This is the first study evaluating pain-like behavior in collagen-induced arthritis model.
- 18 . Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA). Clin. Exp. Immunol. 107(3), 507–512 (1997).
- 19 A store-operated calcium channel inhibitor attenuates collagen-induced arthritis. Br. J. Pharmacol. 172(12), 2991–3002 (2015).
- 20 Antinociceptive effects of tumor necrosis factor alpha neutralization in a rat model of antigen-induced arthritis: evidence of a neuronal target. Arthritis Rheum. 58(8), 2368–2378 (2008).
- 21 The role of interleukin-1β in arthritic pain: main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis. Arthritis Rheum. 64(12), 3897–3907 (2012).
- 22 Role of cytokines in mediating mechanical hypernociception in a model of delayed-type hypersensitivity in mice. Eur. J. Pain 12(8), 1059–1068 (2008).
- 23 IL-17 mediates articular hypernociception in antigen-induced arthritis in mice. Pain 148(2), 247–256 (2010).
- 24 IL-33 mediates antigen-induced cutaneous and articular hypernociception in mice. Proc. Natl Acad. Sci. USA 105(7), 2723–2728 (2008).
- 25 Interleukin-17 sensitizes joint nociceptors to mechanical stimuli and contributes to arthritic pain through neuronal interleukin-17 receptors in rodents. Arthritis Rheum. 64(12), 4125–4134 (2012).
- 26 Cooperative role of tumour necrosis factor-α, interleukin-1β and neutrophils in a novel behavioural model that concomitantly demonstrates articular inflammation and hypernociception in mice. Br. J. Pharmacol. 162(1), 72–83 (2011).
- 27 . Monoarticular antigen-induced arthritis leads to pronounced bilateral upregulation of the expression of neurokinin 1 and bradykinin 2 receptors in dorsal root ganglion neurons of rats. Arthritis Res. 2(5), 424–427 (2000).
- 28 . Endothelin receptors and pain. J. Pain 10(1), 4–28 (2009).
- 29 . Effects of differently activated rodent macrophages on sensory neurons: implications for arthritis pain. Arthritis Rheumatol. 67(8), 2263–2272 (2015).
- 30 . Experimental arthritis causes tumor necrosis factor-alpha-dependent infiltration of macrophages into rat dorsal root ganglia which correlates with pain-related behavior. Pain 145(1), 151–159 (2009).
- 31 Phenotypic changes in dorsal root ganglion and spinal cord in the collagen antibody-induced arthritis mouse model. J. Comp. Neurol. 523(10), 1505–1528 (2015).
- 32 . Involvement of tachykinins and NK1 receptor in the joint inflammation with collagen type II-specific monoclonal antibody-induced arthritis in mice. J. Nippon. Med. Sch. 79(2), 129–138 (2012).
- 33 Acid-sensing ion channel 3 deficiency increases inflammation but decreases pain behavior in murine arthritis. Arthritis Rheum. 65(5), 1194–1202 (2013).
- 34 . Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis. Pain 151(2), 394–403 (2010). •• This is the first study evaluating pain-like behavior in K/BxN serum transfer model.
- 35 Capsaicin-sensitive sensory nerves exert complex regulatory functions in the serum-transfer mouse model of autoimmune arthritis. Brain Behav. Immun. 45, 50–59 (2015).
- 36 Differential regulatory role of pituitary adenylate cyclase-activating polypeptide in the serum-transfer arthritis model. Arthritis Rheumatol. 66(10), 2739–2750 (2014).
- 37 . Spinal cathepsin S and fractalkine contribute to chronic pain in the collagen-induced arthritis model. Arthritis Rheum. 64(6), 2038–2047 (2012).
- 38 . Calcitonin gene-related peptide expressing sensory neurons and spinal microglial reactivity contribute to pain states in collagen-induced arthritis. Arthritis Rheumatol. 67(6), 1668–1677 (2015).
- 39 . Involvement of peripheral and spinal tumor necrosis factor α in spinal cord hyperexcitability during knee joint inflammation in rats. Arthritis Rheumatol. 66(3), 599–609 (2014).
- 40 Spinal tumor necrosis factor alpha neutralization reduces peripheral inflammation and hyperalgesia and suppresses autonomic responses in experimental arthritis: a role for spinal tumor necrosis factor alpha during induction and maintenance of peripheral inflammation. Arthritis Rheum. 62(5), 1308–1318 (2010).
- 41 Collagen antibody-induced arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency. Arthritis Rheum. 64(12), 3886–3896 (2012). •• This is the first study evaluating pain-like behavior in collagen antibody-induced arthritis model.
- 42 . Extracellular high-mobility group box 1 protein (HMGB1) as a mediator of persistent pain. Mol. Med. 20, 569–578 (2014).
- 43 Spinal TLR4 mediates the transition to a persistent mechanical hypersensitivity after the resolution of inflammation in serum-transferred arthritis. Pain 152(12), 2881–2891 (2011).
- 44 . Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice. Pharmacol. Biochem. Behav. 99(4), 718–725 (2011).
- 45 Fast modulation of heat-activated ionic current by proinflammatory interleukin 6 in rat sensory neurons. Brain 128(Pt 7), 1634–1641 (2005).
- 46 . Differential effects of locally and systemically administered soluble glycoprotein 130 on pain and inflammation in experimental arthritis. Arthritis Res. Ther. 12(4), R140 (2010).
- 47 . Spinally applied ketamine or morphine attenuate peripheral inflammation and hyperalgesia in acute and chronic phases of experimental arthritis. Brain. Behav. Immun. 24(3), 474–485 (2010).
- 48 . Autoimmunity to type II collagen an experimental model of arthritis. J. Exp. Med. 146(3), 857–868 (1977).
- 49 . Immunisation against heterologous type II collagen induces arthritis in mice. Nature 283(5748), 666–668 (1980).
- 50 . Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates. J. Exp. Med. 154(3), 688–700 (1981).
- 51 . Arthritis in DBA/1 mice induced with passively transferred type II collagen immune serum. Immunohistopathology and serum levels of anti-type II collagen auto-antibodies. Scand. J. Immunol. 31(2), 147–157 (1990).
- 52 . Induction of arthritis with monoclonal antibodies to collagen. J. Immunol. 148(7), 2103–2108 (1992).
- 53 . B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). Clin. Exp. Immunol. 111(3), 521–526 (1998).
- 54 . Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice. Clin. Exp. Immunol. 88(3), 467–472 (1992).
- 55 . Analgesic effect of electroacupuncture on inflammatory pain in the rat model of collagen-induced arthritis: mediation by cholinergic and serotonergic receptors. Brain Res. 1057(1), 181–185 (2005).
- 56 Characterization of N-(adamantan-1-ylmethyl)-5-[(3R-amino-pyrrolidin-1-yl)methyl]-2-chloro-benzamide, a P2X7 antagonist in animal models of pain and inflammation. J. Pharmacol. Exp. Ther. 327(3), 620–633 (2008).
- 57 . Spirulina platensis protects neurons via suppression of glial activation and peripheral sensitization leading to restoration of motor function in collagen-induced arthritic rats. Indian J. Exp. Biol. 49(10), 739–748 (2011).
- 58 . Studies on antigen-induced arthritis in mice. III. Cell and serum transfer experiments. J. Immunol. 118(5), 1645–1648 (1977).
- 59 . Electrical charge of the antigen determines intraarticular antigen handling and chronicity of arthritis in mice. J. Clin. Invest. 74(5), 1850–1859 (1984).
- 60 . Electrical charge of the antigen determines its localization in the mouse knee joint. Deep penetration of cationic BSA in hyaline articular cartilage. Am. J. Pathol. 121(2), 224–234 (1985).
- 61 . Mechanisms of pain in arthritis. Ann. NY Acad. Sci. 966, 343–354 (2002). •• This review paper is covering peripheral and central sensitization mechanisms in inflammation-induced joint pain based on the findings from antigen-induced arthritis model.
- 62 Antigen-induced inflammatory mechanical hypernociception in mice is mediated by IL-18. Brain Behav. Immun. 21(5), 535–543 (2007).
- 63 . Validation of the digital pressure application measurement (PAM) device for detection of primary mechanical hyperalgesia in rat and mouse antigen-induced knee joint arthritis. Methods Find. Exp. Clin. Pharmacol. 32(8), 575–583 (2010).
- 64 . Serum transfer of collagen-induced arthritis in mice. J. Exp. Med. 158(2), 378–392 (1983).
- 65 . Collagen type II-specific monoclonal antibody-induced arthritis in mice: description of the disease and the influence of age, sex, and genes. Am. J. Pathol. 163(5), 1827–1837 (2003).
- 66 . Collagen antibody induced arthritis. Methods Mol. Med. 136, 215–223 (2007).
- 67 Spinal HMGB1 induces TLR4-mediated long-lasting hypersensitivity and glial activation and regulates pain-like behavior in experimental arthritis. Pain 155(9), 1802–1813 (2014).
- 68 . Collagen antibodies induce pain-like behavior in mice without signs of inflammation. Arthritis Rheum. 65, S528–S529 (2013).
- 69 . Organ-specific disease provoked by systemic autoimmunity. Cell 87(5), 811–822 (1996).
- 70 Genetic influences on the end-stage effector phase of arthritis. J. Exp. Med. 194(3), 321–330 (2001).
- 71 . Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science 286(5445), 1732–1735 (1999).
- 72 Critical roles for interleukin 1 and tumor necrosis factor alpha in antibody-induced arthritis. J. Exp. Med. 196(1), 77–85 (2002).
- 73 Arthritogenic monoclonal antibodies from K/BxN mice. J. Exp. Med. 195(8), 1071–1077 (2002).
- 74 From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins. Immunity 10(4), 451–461 (1999).
- 75 . K/BxN serum transfer arthritis as a model of inflammatory joint pain. Methods Mol. Biol. 851, 249–260 (2012).
- 76 Effects of long term polyarthritis and subsequent NSAID treatment on activity with disassociation of tactile allodynia in the mouse. Neurocomputing 84, 47–52 (2012).
- 77 . Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. Pharmacol. Rev. 67(2), 280–309 (2015).
- 78 . Nociceptive neurons detect cytokines in arthritis. Arthritis Res. Ther. 16(5), 470 (2014).
- 79 Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proc. Natl Acad. Sci. USA 108(9), 3731–3736 (2011).
- 80 . Tumour necrosis factor-alpha mediates carrageenin-induced knee-joint incapacitation and also triggers overt nociception in previously inflamed rat knee-joints. Pain 82(1), 81–87 (1999).
- 81 . Cytokine and chemokine regulation of sensory neuron function. Handb. Exp. Pharmacol. (194), 417–449 (2009).
- 82 . Axonal transport of TNF-alpha in painful neuropathy: distribution of ligand tracer and TNF receptors. J. Neuroimmunol. 114(1), 48–56 (2001).
- 83 . Cell-specific expression and lipopolysaccharide-induced regulation of tumor necrosis factor alpha (TNFalpha) and TNF receptors in rat dorsal root ganglion. J. Neurosci. 24(43), 9623–9631 (2004).
- 84 . Spinal nerve ligation induces transient upregulation of tumor necrosis factor receptors 1 and 2 in injured and adjacent uninjured dorsal root ganglia in the rat. Neurosci. Lett. 347(3), 179–182 (2003).
- 85 . The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation. Arthritis. Res. Ther. 7(4), R807–16 (2005).
- 86 . Unraveling the story of NGF-mediated sensitization of nociceptive sensory neurons: ON or OFF the Trks? Mol. Interv. 7(1), 26–41 (2007).
- 87 . Cytokines, nerve growth factor and inflammatory hyperalgesia: the contribution of tumour necrosis factor alpha. Br. J. Pharmacol. 121(3), 417–424 (1997).
- 88 . Preventive and therapeutic anti-TNF-α therapy with pentoxifylline decreases arthritis and the associated periodontal co-morbidity in mice. Life. Sci. 93(9), 423–428 (2013).
- 89 . The pathogenesis of rheumatoid arthritis. N. Engl. J. Med. 365(23), 2205–2219 (2011).
- 90 . Role of the immune system in chronic pain. Nat. Rev. Neurosci. 6(7), 521–532 (2005).
- 91 Expression of interleukin-1 beta in rat dorsal root ganglia. J. Neuroimmunol. 118(2), 203–211 (2001).
- 92 Nociceptors are interleukin-1beta sensors. J. Neurosci. 28(52), 14062–14073 (2008).
- 93 . Cutaneous hyperalgesia induced by peripheral injection of interleukin-1 beta in the rat. Brain Res. 657(1), 133–140 (1994).
- 94 Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur. J. Immunol. 18(11), 1797–1801 (1988).
- 95 . Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting the interleukin-6 receptor. Clin. Ther. 34(4), 788–802 (2012).
- 96 . Spinal interleukin-6 is an amplifier of arthritic pain in the rat. Arthritis Rheum. 64(7), 2233–2242 (2012).
- 97 . Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury. J. Neurochem. 83(1), 100–109 (2002).
- 98 . Satellite glial cells express IL-6 and corresponding signal-transducing receptors in the dorsal root ganglia of rat neuropathic pain model. Neuron Glia Biol. 6(1), 73–83 (2010).
- 99 . Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on heat-evoked calcitonin gene-related peptide release from rat skin. J. Neurosci. 20(16), 6289–6293 (2000).
- 100 . Acute and long-term effects of IL-6 on cultured dorsal root ganglion neurones from adult rat. J. Neurochem. 94(1), 238–248 (2005).
- 101 . Structure and signalling in the IL-17 receptor family. Nat. Rev. Immunol. 9(8), 556–567 (2009).
- 102 . Neuronal IL-17 receptor upregulates TRPV4 but not TRPV1 receptors in DRG neurons and mediates mechanical but not thermal hyperalgesia. Mol. Cell. Neurosci. 52, 152–160 (2013).
- 103 . Prostaglandins and rheumatoid arthritis. Arthritis 2012(5), 239310–239317 (2012).
- 104 The effect of gabapentin and ketorolac on allodynia and conditioned place preference in antibody-induced inflammation. Eur. J. Pain
doi:10.1002/ejp.816 (2015) (Epub ahead of print). - 105 . Increase of galanin-like immunoreactivity in rat dorsal root ganglion cells after peripheral axotomy. Neurosci. Lett. 83(3), 217–220 (1987).
- 106 . Bilateral changes of substance P-, neurokinin A-, calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity in rat knee joint synovial fluid during acute monoarthritis. Neurosci. Lett. 153(1), 37–40 (1993).
- 107 . Upregulation, release and axonal transport of substance P and calcitonin gene-related peptide in adjuvant inflammation and regulatory function of nerve growth factor. Regul. Pept. 46(1), 150–154 (1993).
- 108 . Peptide plasticity in primary sensory neurons and spinal cord during adjuvant-induced arthritis in the rat: an immunocytochemical and in situ hybridization study. Neuroscience 82(2), 575–589 (1998).
- 109 . Expression of neuropeptide Y and neuropeptide Y (Y1) receptor mRNA in rat spinal cord and dorsal root ganglia following peripheral tissue inflammation. J. Neurosci. 14(11 Pt 1), 6423–6434 (1994).
- 110 . Somatostatin and its receptor family. Front. Neuroendocrinol. 20(3), 157–198 (1999).
- 111 Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy. Exp. Neurol. 138(1), 93–104 (1996).
- 112 Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune-mediated arthritis. Arthritis Rheum. 63(8), 2352–2362 (2011).
- 113 Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol. Rev. 61(3), 283–357 (2009).
- 114 . Dissecting the functional significance of endothelin A receptors in peripheral nociceptors in vivo via conditional gene deletion. Pain 148(2), 206–214 (2010).
- 115 . Contribution of peripheral endothelin ETA and ETB receptors in neuropathic pain induced by spinal nerve ligation in rats. Eur. J. Pain 14(9), 911–917 (2010).
- 116 . Expression and localization of endothelin receptors: implications for the involvement of peripheral glia in nociception. J. Neurosci. 21(3), 999–1006 (2001).
- 117 . Potent anti-inflammatory and antinociceptive activity of the endothelin receptor antagonist bosentan in monoarthritic mice. Arthritis Res. Ther. 13(3), R97 (2011).
- 118 . Voltage gated sodium and calcium channel blockers for the treatment of chronic inflammatory pain. Neurosci. Lett. 557(Pt A), 19–26 (2013).
- 119 . Transient receptor potential ion channels in primary sensory neurons as targets for novel analgesics. Br. J. Pharmacol. 171(10), 2508–2527 (2014).
- 120 . Role of ASIC3 in the primary and secondary hyperalgesia produced by joint inflammation in mice. Pain 137(3), 662–669 (2008).
- 121 . Acid-sensing ion channel 3 expression in mouse knee joint afferents and effects of carrageenan-induced arthritis. J. Pain 10(3), 336–342 (2009).
- 122 Evidence for brain glial activation in chronic pain patients. Brain 138(Pt 3), 604–615 (2015).
- 123 . Glia and pain: Is chronic pain a gliopathy? Pain 154(Suppl. 1), 10–28 (2013).
- 124 . Nonneuronal central mechanisms of pain: glia and immune response. Prog. Mol. Biol. Transl. Sci. 131, 325–358 (2015).
- 125 Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat. Neurosci. 18(8), 1081–1083 (2015).
- 126 . The c-Jun N-terminal kinase 1 (JNK1) in spinal astrocytes is required for the maintenance of bilateral mechanical allodynia under a persistent inflammatory pain condition. Pain 148(2), 309–319 (2010).
- 127 Disruption of the blood-brain barrier in collagen-induced arthritic mice. Neurosci. Lett. 482(3), 208–211 (2010).
- 128 Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice. Proc. Natl Acad. Sci. USA 109(31), 12728–12733 (2012).
- 129 . Fractalkine/CX3CR1 signaling during neuropathic pain. Front. Cell. Neurosci. 8, 121 (2014).
- 130 . Role of extracellular damage-associated molecular pattern molecules (DAMPs) as mediators of persistent pain. Prog. Mol. Biol. Transl. Sci. 131, 251–279 (2015).
- 131 . The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain. J. Neuroinflammation 9(1), 180 (2012).
- 132 Neuropathic pain in rats with a partial sciatic nerve ligation is alleviated by intravenous injection of monoclonal antibody to high mobility group box-1. PLoS ONE 8(8), e73640 (2013).
- 133 HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J. Neurosci. 26(24), 6413–6421 (2006).
- 134 Selective proinflammatory activation of astrocytes by high-mobility group box 1 protein signaling. J. Immunol. 179(12), 8525–8532 (2007).
- 135 . Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur. J. Neurosci. 20(2), 467–473 (2004).
- 136 Spinal cord Toll-like receptor 4 mediates inflammatory and neuropathic hypersensitivity in male but not female mice. J. Neurosci. 31(43), 15450–15454 (2011).
- 137 . Endogenous ligands of Toll-like receptors. J. Leukoc. Biol. 76(3), 514–519 (2004).
- 138 . The anti-inflammatory effects of prostaglandins. J. Investig. Med. 57(6), 703–708 (2009).
- 139 . Recent advances in the pharmacological management of acute and chronic pain. Ann. Palliat. Med. 3(4), 263–275 (2014).
- 140 . Ketamine in pain management. CNS Neurosci. Ther. 19(6), 396–402 (2013).
- 141 . Preclinical assessment of pain: improving models in discovery research. Curr. Top. Behav. Neurosci. 20, 101–120 (2014).
- 142 . Neurobiological studies of chronic pain and analgesia: rationale and refinements. Eur. J. Pharmacol. 759, 169–181 (2015).