Skip to main content
Article thumbnail
Location of Repository

Inflammation reduces mechanical thresholds in a population of transient receptor potential channel A1-expressing nociceptors in the rat

By James P Dunham, Sara Kelly and Lucy F Donaldson

Abstract

Inflammatory hypersensitivity is characterized by behavioural reductions in withdrawal thresholds to noxious stimuli. Although cutaneous primary afferent neurones are known to have lowered thermal thresholds in inflammation, whether their mechanical thresholds are altered remains controversial. The transient receptor potential channel A1 (TRPA1) is a receptor localized to putative nociceptive neurones and is implicated in mechanical and thermal nociception. Herein, we examined changes in the properties of single primary afferents in normal and acutely inflamed rats and determined whether specific nociceptive properties, particularly mechanical thresholds, are altered in the subpopulation of afferents that responded to the TRPA1 agonist cinnamaldehyde (TRPA1-positive afferents). TRPA1-positive afferents in normal animals belonged to the mechanonociceptive populations, many of which also responded to heat or capsaicin but only a few of which responded to cold. In acute inflammation, a greater proportion of afferents responded to cinnamaldehyde and an increased proportion of dorsal root ganglion neurones expressed TRPA1 protein. Functionally, in inflammation, TRPA1-positive afferents showed significantly reduced mechanical thresholds and enhanced activity to agonist stimulation. Inflammation altered thermal thresholds in both TRPA1-positive and TRPA1-negative afferents. Our data show that a subset of afferents is sensitized to mechanical stimulation by inflammation and that these afferents are defined by expression of TRPA1

Topics: Research Reports
Publisher: Blackwell Publishing Ltd
OAI identifier: oai:pubmedcentral.nih.gov:2658012
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (2007). 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1.
    2. (1993). A discrete adjuvantinduced monoarthritis in the rat: effects of adjuvant dose.
    3. (2004). A model of periodontitis in the rat: effect of lipopolysaccharide on bone resorption, osteoclast activity, and local peptidergic innervation.
    4. (2007). A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition.
    5. (2008). ª The Authors
    6. (1951). Action potentials of cold fibres and intracutaneous temperature gradient.
    7. (2007). Activation of TRPA1 channel facilitates excitatory synaptic transmission in substantia gelatinosa neurons of the adult rat spinal cord.
    8. (2006). An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.
    9. (2004). An assessment of vascular pain using the flexor reflex in anesthetized rats.
    10. (2006). Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain.
    11. (2003). ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures.
    12. (2007). Arthritis model, adjuvantinduced arthritis.
    13. (1997). C-fiber mechanical stimulusresponse functions are different in inflammatory versus neuropathic hyperalgesia in the rat.
    14. (2006). Cannabinoid WIN 55,212-2 regulates TRPV1 phosphorylation in sensory neurons.
    15. (1992). Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin.
    16. (1990). Carrageenan inflammation increases bradykinin sensitivity of rat cutaneous nociceptors.
    17. (2002). Characterization of Adelta- and C-fibers innervating the plantar rat hindpaw one day after an incision.
    18. (1993). Chemosensitivity and sensitization of nociceptive afferents that innervate the hairy skin of monkey.
    19. (2007). Cold sensitivity of recombinant TRPA1 channels.
    20. (2005). Conservation of functional and pharmacological properties in the distantly related temperature sensors TRVP1 and TRPM8.
    21. (1993). Cutaneous sensory receptors in the rat foot.
    22. (2000). Cyclooxygenase 1 is a marker for a subpopulation of putative nociceptive neurons in rat dorsal root ganglia.
    23. (1986). Does neurogenic inflammation alter the sensitivity of unmyelinated nociceptors in the rat?
    24. (1985). Effects of an experimental arthritis on the sensory properties of fine articular afferent units.
    25. (2007). Homologous and heterologous desensitization of capsaicin and mustard oil responses utilize different cellular pathways in nociceptors.
    26. (2004). Integrin signaling in inflammatory and neuropathic pain in the rat.
    27. (1987). Leukotriene and prostaglandin sensitization of cutaneous high-threshold Cand A-delta mechanonociceptors in the hairy skin of rat hindlimbs.
    28. (1988). Leukotriene B4 decreases the mechanical and thermal thresholds of C-fiber nociceptors in the hairy skin of the rat.
    29. (2006). Many cold sensitive peripheral neurons of the mouse do not express TRPM8 or TRPA1.
    30. (1999). Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat.
    31. (1986). Mechanical sensitivity of group III and IV afferents from posterior articular nerve in normal and inflamed cat knee.
    32. (1999). Mechanical sensitization of cutaneous C-fiber nociceptors by prostaglandin E2 in the rat.
    33. (2004). Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1.
    34. (1999). Neural response of mechanoreceptors to acute inflammation in the rotator cuff of the shoulder joint in rabbits.
    35. (1999). Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin.
    36. (2007). NGF up-regulates TRPA1: implications for orofacial pain.
    37. (2005). Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and hearing.
    38. (1995). Novel classes of responsive and unresponsive C nociceptors in human skin.
    39. (2004). Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin.
    40. (2006). Pathophysiology and treatment of pain in joint disease.
    41. (1982). Primary afferent units from the hairy skin of the rat hind limb.
    42. (1977). Primate cutaneous sensory units with unmyelinated (C) afferent fibers.
    43. (1991). Properties of high-threshold mechanoreceptors in the oral mucosa.
    44. (2005). Pungent products from garlic activate the sensory ion channel TRPA1.
    45. (1998). Recordings of human polymodal single C-fiber afferents following mechanical and argon-laser heat stimulation of inflamed skin.
    46. (1997). Responses of cutaneous A-fiber nociceptors to noxious cold.
    47. (1997). Responses of primary afferents and spinal dorsal horn neurons to thermal and mechanical stimuli before and during zymosan-induced inflammation of the rat hindpaw.
    48. Responses to dynamic and static pressure.
    49. (1992). Responsiveness and functional attributes of electrically localized terminals of cutaneous C-fibers in vivo and in vitro.
    50. (2004). Responsiveness of C-fiber nociceptors to punctate force-controlled stimuli in isolated rat skin: lack of modulation by inflammatory mediators and flurbiprofen.
    51. (1994). Sensitization of high mechanothreshold superficial dorsal horn and flexor motor neurones following chemosensitive primary afferent activation.
    52. (2007). Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain.
    53. (2007). Sensory nerves have altered function contralateral to a monoarthritis and may contribute to the symmetrical spread of inflammation.
    54. (1985). Sensory receptors in ankle joint capsules of normal and arthritic rats.
    55. (1996). Silent afferents: a separate class of primary afferents?
    56. (2006). Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors.
    57. (1999). The changing sensitivity in the life of the nociceptor.
    58. (1993). The effect of capsaicin and conventional analgesics in two models of monoarthritis in the rat. Agents Actions, 38 Spec No,
    59. (1991). The role of PGE2 in the sensitization of mechanoreceptors in normal and inflamed ankle joints of the rat.
    60. (1981). Thermoregulation and Temperature Regulation.
    61. (2007). Transient receptor potential TRPA1 channel desensitization in sensory neurons is agonist dependent and regulated by TRPV1-directed internalization.
    62. (2005). TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol.
    63. (2006). TRPA1 contributes to cold, mechanical, and chemical nociception but is not essential for hair-cell transduction.
    64. (2005). TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury.
    65. (2004). TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells.
    66. (2007). TRPA1 is differentially modulated by the amphiphatic molecules trinitrophenol and chlorpromazine.
    67. (2007). TRPA1 mediates formalin-induced pain.
    68. (2006). TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents.
    69. (2005). TRPA1-expressing sensory afferent properties in inflammation 3159 ª The Authors (2008). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd European
    70. (2000). Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.