trpm cation channels


Summary: A subgroup of TRP cation channels named after melastatin protein. They have the TRP domain but lack ANKYRIN repeats. Enzyme domains in the C-terminus leads to them being called chanzymes.

Top Publications

  1. Naziroglu M. TRPM2 channel membrane currents in primary rat megakaryocytes were activated by the agonist ADP-ribose but not oxidative stress. J Membr Biol. 2011;241:51-7 pubmed publisher
    ..Activation of TRPM2 channels in megakaryocytes seems to be intracellular and ADPR-dependent...
  2. Knowles H, Heizer J, Li Y, Chapman K, Ogden C, Andreasen K, et al. Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity against Listeria monocytogenes. Proc Natl Acad Sci U S A. 2011;108:11578-83 pubmed publisher
    ..These findings establish an unsuspected role for ADP-ribose and ROS-mediated cation flux for innate immunity, opening up unique possibilities for immunomodulatory intervention through TRPM2. ..
  3. Uchida K, Tominaga M. TRPM2 modulates insulin secretion in pancreatic ?-cells. Islets. 2011;3:209-11 pubmed
    ..Although further examination is needed to clarify the mechanism of TRPM2-mediated insulin secretion, TRPM2 may be a key player in regulation of insulin secretion and could represent a new target for diabetes therapy. ..
  4. Belrose J, Xie Y, Gierszewski L, MacDonald J, Jackson M. Loss of glutathione homeostasis associated with neuronal senescence facilitates TRPM2 channel activation in cultured hippocampal pyramidal neurons. Mol Brain. 2012;5:11 pubmed publisher
    ..This interaction may play an important role in aging and neurological diseases associated with depletion of GSH. ..
  5. Pertusa M, Madrid R, Morenilla Palao C, Belmonte C, Viana F. N-glycosylation of TRPM8 ion channels modulates temperature sensitivity of cold thermoreceptor neurons. J Biol Chem. 2012;287:18218-29 pubmed publisher
  6. Chen H, Su L, González Pagán O, Overton J, Runnels L. A key role for Mg(2+) in TRPM7's control of ROS levels during cell stress. Biochem J. 2012;445:441-8 pubmed publisher
    ..Taken together, these data uncover an essential role for Mg(2+) in TRPM7's control of cell survival and in the regulation of cellular ROS levels. ..
  7. Yu P, Zhang Z, Hao B, Zhao Y, Zhang L, Lee H, et al. A novel fluorescent cell membrane-permeable caged cyclic ADP-ribose analogue. J Biol Chem. 2012;287:24774-83 pubmed publisher
    ..In summary, our results indicate that uncaging of Co-i-cIDPRE incites Ca(2+) release from endoplasmic reticulum via RyRs and triggers Ca(2+) influx via TRPM2. ..
  8. Chen G, Zeng B, Eastmond S, Elsenussi S, Boa A, Xu S. Pharmacological comparison of novel synthetic fenamate analogues with econazole and 2-APB on the inhibition of TRPM2 channels. Br J Pharmacol. 2012;167:1232-43 pubmed publisher
    ..The fenamate analogue 3-MFA was more selective than other TRPM2 channel blockers. FFA, 2-APB and econazole should be used with caution as TRPM2 channel blockers, as these compounds can interfere with intracellular Ca(2+) movement. ..
  9. Peachey N, Pearring J, Bojang P, Hirschtritt M, Sturgill Short G, Ray T, et al. Depolarizing bipolar cell dysfunction due to a Trpm1 point mutation. J Neurophysiol. 2012;108:2442-51 pubmed publisher
    ..The Trpm1(tvrm27/tvrm27) mutant will be useful for elucidating the role of TRPM1 in DBC signal transduction, for determining how Trpm1 mutations impact central visual processing, and for evaluating experimental therapies for cCSNB...

More Information


  1. Knowles H, Li Y, Perraud A. The TRPM2 ion channel, an oxidative stress and metabolic sensor regulating innate immunity and inflammation. Immunol Res. 2013;55:241-8 pubmed publisher
    ..Understanding TRPM2's complex involvement in inflammation is crucial to evaluating the potential of manipulating TRPM2 activity and ADPR metabolism for therapeutic intervention. ..
  2. Devi S, Markandeya Y, Maddodi N, Dhingra A, Vardi N, Balijepalli R, et al. Metabotropic glutamate receptor 6 signaling enhances TRPM1 calcium channel function and increases melanin content in human melanocytes. Pigment Cell Melanoma Res. 2013;26:348-56 pubmed publisher
    ..These data suggest differences in coupling of TRPM1 function to mGluR6 signaling explain different cellular responses to glutamate in the retina and the skin...
  3. Simard C, Sallé L, Rouet R, Guinamard R. Transient receptor potential melastatin 4 inhibitor 9-phenanthrol abolishes arrhythmias induced by hypoxia and re-oxygenation in mouse ventricle. Br J Pharmacol. 2012;165:2354-64 pubmed publisher
    ..9-Phenanthrol abolished EADs, which strongly suggests the involvement of TRPM4 in the generation of EAD. This identifies non-selective cation channels inhibitors as new pharmacological candidates in the treatment of arrhythmias. ..
  4. Keh S, Facer P, Yehia A, Sandhu G, Saleh H, Anand P. The menthol and cold sensation receptor TRPM8 in normal human nasal mucosa and rhinitis. Rhinology. 2011;49:453-7 pubmed publisher
    ..We show that TRPM8 nerve fibres are abundant in nasal mucosa particularly around blood vessels, and may mediate neurovascular reflexes. TRPM8 antagonists deserve consideration for therapeutic trial in rhinitis. ..
  5. Bellone R, Holl H, Setaluri V, Devi S, Maddodi N, Archer S, et al. Evidence for a retroviral insertion in TRPM1 as the cause of congenital stationary night blindness and leopard complex spotting in the horse. PLoS ONE. 2013;8:e78280 pubmed publisher
    ..This study represents the first description of an LTR insertion being associated with both a pigmentation phenotype and an eye disorder. ..
  6. Zierler S, Yao G, Zhang Z, Kuo W, Porzgen P, Penner R, et al. Waixenicin A inhibits cell proliferation through magnesium-dependent block of transient receptor potential melastatin 7 (TRPM7) channels. J Biol Chem. 2011;286:39328-35 pubmed publisher
  7. Sarria I, Ling J, Zhu M, Gu J. TRPM8 acute desensitization is mediated by calmodulin and requires PIP(2): distinction from tachyphylaxis. J Neurophysiol. 2011;106:3056-66 pubmed publisher
    ..Thus, through gating modulation, Ca(2+)-calmodulin provides a mechanism to rapidly regulate TRPM8 functions in the somatosensory system. ..
  8. Klooster J, Blokker J, ten Brink J, Unmehopa U, Fluiter K, Bergen A, et al. Ultrastructural localization and expression of TRPM1 in the human retina. Invest Ophthalmol Vis Sci. 2011;52:8356-62 pubmed publisher
    ..In the human retina TRPM1 is expressed on ON-bipolar cell dendrites that invaginate photoreceptor terminals. TRPM1 is also expressed on the synaptic ribbons of a subclass of rods, suggesting a dual function for TRPM1 in the ON-pathway. ..
  9. Uchida K, Tominaga M. The role of thermosensitive TRP (transient receptor potential) channels in insulin secretion. Endocr J. 2011;58:1021-8 pubmed
  10. Naziroglu M, Ozgül C, Ciğ B, Doğan S, Uğuz A. Glutathione modulates Ca(2+) influx and oxidative toxicity through TRPM2 channel in rat dorsal root ganglion neurons. J Membr Biol. 2011;242:109-18 pubmed publisher
    ..Since cytosolic glutathione depletion is a common feature of neuropathic pain and diseases of sensory neuron, our findings are relevant to the etiology of neuropathology in DRG neurons. ..
  11. Widmayer P, Breer H, Hass N. Candidate chemosensory cells in the porcine stomach. Histochem Cell Biol. 2011;136:37-45 pubmed publisher
    ..These results indicate substantial differences regarding the phenotype of candidate chemosensory cells of mice and swine and underline the importance of choosing the most suitable model organisms. ..
  12. Shapovalov G, Lehen kyi V, Skryma R, Prevarskaya N. TRP channels in cell survival and cell death in normal and transformed cells. Cell Calcium. 2011;50:295-302 pubmed publisher
    ..This review focuses on the aspects of TRP channel localization and function that affect the balance between cell survival and death and how various dysregulations of these channels may lead to perturbed balance and onset of cancer. ..
  13. Magnone M, Bauer I, Poggi A, Mannino E, Sturla L, Brini M, et al. NAD+ levels control Ca2+ store replenishment and mitogen-induced increase of cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 channel gating in human T lymphocytes. J Biol Chem. 2012;287:21067-81 pubmed publisher
    ..Finally, the presence of NAD(+) precursors up-regulated important T cell functions, such as proliferation and IL-2 release in response to mitogens. ..
  14. Tamayo N, Bo Y, Gore V, Ma V, Nishimura N, Tang P, et al. Fused piperidines as a novel class of potent and orally available transient receptor potential melastatin type 8 (TRPM8) antagonists. J Med Chem. 2012;55:1593-611 pubmed publisher
    ..Compound 87 demonstrated target coverage in vivo after oral administration in a rat pharmacodynamic model measuring the prevention of icilin-induced wet-dog shakes (WDS). ..
  15. Thilo F, Vorderwülbecke B, Marki A, Krueger K, Liu Y, Baumunk D, et al. Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells. Hypertension. 2012;59:1232-40 pubmed publisher
  16. Sala Rabanal M, Wang S, Nichols C. On potential interactions between non-selective cation channel TRPM4 and sulfonylurea receptor SUR1. J Biol Chem. 2012;287:8746-56 pubmed publisher
    ..2 and SUR1, whereas there was no detectable FRET efficiency between TRPM4 and SUR1. Our data suggest that functional or structural association of TRPM4 and SUR1 is unlikely...
  17. Zhang Z, Zhang W, Jung D, Ko H, Lee Y, Friedline R, et al. TRPM2 Ca2+ channel regulates energy balance and glucose metabolism. Am J Physiol Endocrinol Metab. 2012;302:E807-16 pubmed publisher
    ..Our findings identify a novel role of TRPM2 Ca(2+) channel in the regulation of energy expenditure, inflammation, and insulin resistance. ..
  18. Chubanov V, Mederos y Schnitzler M, Meisner M, Schafer S, Abstiens K, Hofmann T, et al. Natural and synthetic modulators of SK (K(ca)2) potassium channels inhibit magnesium-dependent activity of the kinase-coupled cation channel TRPM7. Br J Pharmacol. 2012;166:1357-76 pubmed publisher
    ..1-2.3 channels. NS8593 acts as a negative gating modulator of TRPM7 and is well-suited to study functional features and cellular roles of endogenous TRPM7. ..
  19. Kim T, Shin S, Song M, Lee J, Park K. Identification of the phosphorylation sites on intact TRPM7 channels from mammalian cells. Biochem Biophys Res Commun. 2012;417:1030-4 pubmed publisher
    ..The present results show that TRPM7 channels are phosphorylated at multiple sites, which serves as a mechanism to modulate the dynamic functions of TRPM7 channels in mammalian cells. ..
  20. Kondo M, Sanuki R, Ueno S, Nishizawa Y, Hashimoto N, Ohguro H, et al. Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction. PLoS ONE. 2011;6:e19911 pubmed publisher
    ..The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction...
  21. Yang W, Manna P, Zou J, Luo J, Beech D, Sivaprasadarao A, et al. Zinc inactivates melastatin transient receptor potential 2 channels via the outer pore. J Biol Chem. 2011;286:23789-98 pubmed publisher
    ..We conclude from these results that Zn(2+) inactivates the TRPM2 channels and that residues in the outer pore are critical determinants of the inactivation. ..
  22. Xie Y, Belrose J, Lei G, Tymianski M, Mori Y, MacDonald J, et al. Dependence of NMDA/GSK-3? mediated metaplasticity on TRPM2 channels at hippocampal CA3-CA1 synapses. Mol Brain. 2011;4:44 pubmed publisher
    ..Notably, LTD could be rescued in TRPM2 null mice by recruitment of GSK-3? signaling following dopamine D2 receptor stimulation. We propose that TRPM2 channels play a key role in hippocampal synaptic plasticity. ..
  23. Baldoli E, Maier J. Silencing TRPM7 mimics the effects of magnesium deficiency in human microvascular endothelial cells. Angiogenesis. 2012;15:47-57 pubmed publisher
    ..Our results point to magnesium and TRPM7 as a modulators of the angiogenic phenotype of microvascular endothelial cells. ..
  24. Dhennin Duthille I, Gautier M, Faouzi M, Guilbert A, Brevet M, Vaudry D, et al. High expression of transient receptor potential channels in human breast cancer epithelial cells and tissues: correlation with pathological parameters. Cell Physiol Biochem. 2011;28:813-22 pubmed publisher
    ..The high expression of TRP channels in tumors suggests the potential of these channels for diagnostic, prognosis and/or therapeutic approaches in human breast ductal adenocarcinoma. ..
  25. Becerra A, Echeverria C, Varela D, Sarmiento D, Armisen R, Nuñez Villena F, et al. Transient receptor potential melastatin 4 inhibition prevents lipopolysaccharide-induced endothelial cell death. Cardiovasc Res. 2011;91:677-84 pubmed publisher
    ..These results are useful in sepsis drug design and development of new strategies for sepsis therapy. ..
  26. Vriens J, Owsianik G, Hofmann T, Philipp S, Stab J, Chen X, et al. TRPM3 is a nociceptor channel involved in the detection of noxious heat. Neuron. 2011;70:482-94 pubmed publisher
    ..These experiments reveal an unanticipated role for TRPM3 as a thermosensitive nociceptor channel implicated in the detection of noxious heat. ..
  27. Nuñez Villena F, Becerra A, Echeverria C, Briceño N, Porras O, Armisen R, et al. Increased expression of the transient receptor potential melastatin 7 channel is critically involved in lipopolysaccharide-induced reactive oxygen species-mediated neuronal death. Antioxid Redox Signal. 2011;15:2425-38 pubmed publisher
    ..We conclude that LPS promotes an abnormal ROS-dependent TRPM7 overexpression, which plays a crucial role in pathologic events, thus leading to neuronal dysfunction and death. ..
  28. Zeng B, Chen G, Xu S. Divalent copper is a potent extracellular blocker for TRPM2 channel. Biochem Biophys Res Commun. 2012;424:279-84 pubmed publisher
    ..We concluded that Cu(2+) is a potent TRPM2 channel blocker. The sensitivity of TRPM2 channel to heavy metal ions could be a new mechanism for the pathogenesis of some metal ion-related diseases. ..
  29. Abriel H, Syam N, Sottas V, Amarouch M, Rougier J. TRPM4 channels in the cardiovascular system: physiology, pathophysiology, and pharmacology. Biochem Pharmacol. 2012;84:873-81 pubmed publisher
    ..Based on recent findings, the TRPM4 channel can be proposed as a future target for the pharmacological treatment of cardiovascular disorders, such as hypertension and cardiac arrhythmias...
  30. Toth B, CSANADY L. Pore collapse underlies irreversible inactivation of TRPM2 cation channel currents. Proc Natl Acad Sci U S A. 2012;109:13440-5 pubmed publisher
    ..The noninactivating TRPM2 variant will be invaluable for gating studies. ..
  31. Robbins A, Kurose M, Winterson B, Meng I. Menthol activation of corneal cool cells induces TRPM8-mediated lacrimation but not nociceptive responses in rodents. Invest Ophthalmol Vis Sci. 2012;53:7034-42 pubmed publisher
    ..The purpose of our study was to determine whether menthol induces corneal cool cell activity and lacrimation via the transient receptor potential melastatin-8 (TRPM8) channel without evoking nociceptive responses...
  32. Knowlton W, Palkar R, Lippoldt E, McCoy D, Baluch F, Chen J, et al. A sensory-labeled line for cold: TRPM8-expressing sensory neurons define the cellular basis for cold, cold pain, and cooling-mediated analgesia. J Neurosci. 2013;33:2837-48 pubmed publisher
    ..Together, these data show that, although some limited cold sensitivity remains in Trpm8(-/-) mice, TRPM8 neurons are required for the breadth of behavioral responses evoked by cold temperatures. ..
  33. Cao Y, Posokhova E, Martemyanov K. TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6-dependent manner. J Neurosci. 2011;31:11521-6 pubmed publisher
  34. Harrington A, Hughes P, Martin C, Yang J, Castro J, Isaacs N, et al. A novel role for TRPM8 in visceral afferent function. Pain. 2011;152:1459-68 pubmed publisher
    ..TRPM8 is present on a select population of colonic high threshold sensory neurons, which may also co-express TRPV1. TRPM8 couples to TRPV1 and TRPA1 to inhibit their downstream chemosensory and mechanosensory actions. ..
  35. Deason Towne F, Perraud A, Schmitz C. The Mg2+ transporter MagT1 partially rescues cell growth and Mg2+ uptake in cells lacking the channel-kinase TRPM7. FEBS Lett. 2011;585:2275-8 pubmed publisher
    ..Furthermore, overexpression of MagT1 in TRPM7(-/-) cells augments their capacity to uptake Mg(2+), and improves their growth behavior in the absence of excess Mg(2+). ..
  36. Hughes S, Pothecary C, Jagannath A, Foster R, Hankins M, Peirson S. Profound defects in pupillary responses to light in TRPM-channel null mice: a role for TRPM channels in non-image-forming photoreception. Eur J Neurosci. 2012;35:34-43 pubmed publisher
    ..Expression of TRPM3 is detected in Muller cells and the ciliary body but is absent from pRGCs, and thus our data support an indirect role for TRPM3 in pupillary light responses. ..
  37. Simard J, Tsymbalyuk O, Keledjian K, Ivanov A, Ivanova S, Gerzanich V. Comparative effects of glibenclamide and riluzole in a rat model of severe cervical spinal cord injury. Exp Neurol. 2012;233:566-74 pubmed publisher
    ..Differences in specificity, dose-limiting potency, or in spectrum of action may account for the apparent superiority of glibenclamide over riluzole in this model of severe SCI. ..
  38. Thompson J, Salcedo E, Restrepo D, Finger T. Second-order input to the medial amygdala from olfactory sensory neurons expressing the transduction channel TRPM5. J Comp Neurol. 2012;520:1819-30 pubmed publisher
  39. Knowlton W, Daniels R, Palkar R, McCoy D, McKemy D. Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS ONE. 2011;6:e25894 pubmed publisher
    ..Thus PBMC is an attractive compound that serves as a template for the formulation of highly specific and potent TRPM8 antagonists that will have utility both in vitro and in vivo. ..
  40. Xu S, Chisholm A. A G?q-Ca²? signaling pathway promotes actin-mediated epidermal wound closure in C. elegans. Curr Biol. 2011;21:1960-7 pubmed publisher
    ..elegans triggers a Ca(2+)-dependent signaling cascade that promotes wound closure, in parallel to the innate immune response to damage. Wound closure requires actin polymerization and is negatively regulated by nonmuscle myosin. ..
  41. Sumoza Toledo A, Lange I, Cortado H, Bhagat H, Mori Y, Fleig A, et al. Dendritic cell maturation and chemotaxis is regulated by TRPM2-mediated lysosomal Ca2+ release. FASEB J. 2011;25:3529-42 pubmed publisher
    ..These results highlight TRPM2 as a key player regulating DC chemotaxis through its function as Ca(2+) release channel and confirm ADP-ribose as a novel second messenger for intracellular Ca(2+) mobilization. ..
  42. Baldoli E, Castiglioni S, Maier J. Regulation and function of TRPM7 in human endothelial cells: TRPM7 as a potential novel regulator of endothelial function. PLoS ONE. 2013;8:e59891 pubmed publisher
    ..Our results indicate that TRPM7 modulates endothelial behavior and that any condition leading to TRPM7 upregulation might impair endothelial function. ..
  43. Gao H, Chen X, Du X, Guan B, Liu Y, Zhang H. EGF enhances the migration of cancer cells by up-regulation of TRPM7. Cell Calcium. 2011;50:559-68 pubmed publisher
    ..Thus it seems that TRPM7 plays a pivotal role in the migration of A549 cells induced by EGF and thus could be a potential therapeutic target in lung cancers. ..
  44. Melzer N, Hicking G, Göbel K, Wiendl H. TRPM2 cation channels modulate T cell effector functions and contribute to autoimmune CNS inflammation. PLoS ONE. 2012;7:e47617 pubmed publisher
    ..Our findings suggest TRPM2 cation channels as a potential target for treating autoimmune CNS inflammation. ..
  45. Ledeganck K, Boulet G, Horvath C, Vinckx M, Bogers J, Van Den Bossche R, et al. Expression of renal distal tubule transporters TRPM6 and NCC in a rat model of cyclosporine nephrotoxicity and effect of EGF treatment. Am J Physiol Renal Physiol. 2011;301:F486-93 pubmed publisher
    ..These data suggest that CsA treatment affects Mg(2+) homeostasis via the downregulation of TRPM6 in the DCT. Furthermore, CsA downregulates the NCC in the DCT, associated with an inactivation of the RAAS, resulting in renal sodium loss. ..
  46. Frühwald J, Camacho Londoño J, Dembla S, Mannebach S, Lis A, Drews A, et al. Alternative splicing of a protein domain indispensable for function of transient receptor potential melastatin 3 (TRPM3) ion channels. J Biol Chem. 2012;287:36663-72 pubmed publisher
    ..We conclude that TRPM3?ICF variants are regulatory channel subunits fine-tuning TRPM3 channel activity. ..
  47. Di A, Gao X, Qian F, Kawamura T, Han J, Hecquet C, et al. The redox-sensitive cation channel TRPM2 modulates phagocyte ROS production and inflammation. Nat Immunol. 2011;13:29-34 pubmed publisher
    ..As ROS also activate TRPM2, our findings establish a negative feedback mechanism for the inactivation of ROS production through inhibition of the membrane potential-sensitive NADPH oxidase. ..
  48. Simard J, Woo S, Gerzanich V. Transient receptor potential melastatin 4 and cell death. Pflugers Arch. 2012;464:573-82 pubmed publisher
    ..Future studies will be needed to determine whether TRPM4 also plays a role in regulated necrosis and apoptosis. ..
  49. Jin J, Wu L, Jun J, Cheng X, Xu H, Andrews N, et al. The channel kinase, TRPM7, is required for early embryonic development. Proc Natl Acad Sci U S A. 2012;109:E225-33 pubmed publisher
    ..The in vivo and in vitro results demonstrate a temporal requirement for the Trpm7 channel kinase during embryogenesis. ..
  50. Takahashi N, Kozai D, Kobayashi R, Ebert M, Mori Y. Roles of TRPM2 in oxidative stress. Cell Calcium. 2011;50:279-87 pubmed publisher
    ..In this review, we summarize mechanisms underlying activation of TRPM2 channels by oxidative stress and downstream biological responses, and discuss the biological importance of oxidative stress-activated TRP channels. ..
  51. Wolf F, Trapani V. MagT1: a highly specific magnesium channel with important roles beyond cellular magnesium homeostasis. Magnes Res. 2011;24:S86-91 pubmed publisher
    ..As our knowledge of magnesium advances, it becomes increasingly clear that a deeper understanding of magnesium homeostasis is the key for a deeper insight into relevant pathophysiological conditions, and their treatment. ..
  52. Almeida M, Hew Butler T, Soriano R, Rao S, Wang W, Wang J, et al. Pharmacological blockade of the cold receptor TRPM8 attenuates autonomic and behavioral cold defenses and decreases deep body temperature. J Neurosci. 2012;32:2086-99 pubmed publisher
    ..M8-B affected all thermoeffectors studied (thermopreferendum, tail-skin vasoconstriction, and brown fat thermogenesis), thus suggesting that TRPM8 is a universal cold receptor in the thermoregulation system. ..
  53. Haraguchi K, Kawamoto A, Isami K, Maeda S, Kusano A, Asakura K, et al. TRPM2 contributes to inflammatory and neuropathic pain through the aggravation of pronociceptive inflammatory responses in mice. J Neurosci. 2012;32:3931-41 pubmed publisher
    ..Together, these results suggest that TRPM2 expressed in macrophages and microglia aggravates peripheral and spinal pronociceptive inflammatory responses and contributes to the pathogenesis of inflammatory and neuropathic pain. ..