RGD Reference Report - Protease-activated receptor-1 and platelet-derived growth factor in spinal cord neurons are implicated in neuropathic pain after nerve injury. - Rat Genome Database

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Protease-activated receptor-1 and platelet-derived growth factor in spinal cord neurons are implicated in neuropathic pain after nerve injury.

Authors: Narita, M  Usui, A  Narita, M  Niikura, K  Nozaki, H  Khotib, J  Nagumo, Y  Yajima, Y  Suzuki, T 
Citation: Narita M, etal., J Neurosci. 2005 Oct 26;25(43):10000-9.
RGD ID: 7387272
Pubmed: PMID:16251448   (View Abstract at PubMed)
PMCID: PMC6725566   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.2507-05.2005   (Journal Full-text)

Recently, it has been reported that both thrombin-sensitive protease-activated receptor 1 (PAR-1) and platelet-derived growth factor (PDGF) are present not only in platelets, but also in the CNS, which indicates that they have various physiological functions. In this study, we evaluated whether PAR-1/PDGF in the spinal cord could contribute to the development of a neuropathic pain-like state in mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were significantly suppressed by repeated intrathecal injection of hirudin, which is characterized as a specific and potent thrombin inhibitor. Furthermore, a single intrathecal injection of thrombin produced long-lasting hyperalgesia and allodynia, and these effects were also inhibited by hirudin in normal mice. In nerveligated mice, the increase in the binding of [35S]GTPgammaS to membranes of the spinal cord induced by thrombin and PAR-1-like immunoreactivity (IR) in the spinal cord were each greater than those in sham-operated mice. Thermal hyperalgesia and tactile allodynia induced by sciatic nerve ligation were also suppressed by repeated intrathecal injection of either the PDGF alpha receptor (PDGFRalpha)/Fc chimera protein or the PDGFR-dependent tyrosine kinase inhibitor AG17 [(3,5-di-tert-butyl-4-hydroxybenzylidene)-malononitrile]. Moreover, thermal hyperalgesia and tactile allodynia induced by thrombin in normal mice were virtually eliminated by intrathecal pretreatment with PDGFRalpha/Fc. In immunohistochemical studies, PAR-1-like IR-positive cells in the spinal dorsal horn were mostly colocated on PDGF-like IR-positive neuronal cells. These data provide novel evidence that PAR-1 and PDGF-A-mediated signaling pathway within spinal cord neurons may be directly implicated in neuropathic pain after nerve injury in mice.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hyperalgesia  ISOF2 (Mus musculus)7387272; 7387272associated with Sciatic NeuropathyRGD 
Hyperalgesia  IMP 7387272associated with Sciatic NeuropathyRGD 

Objects Annotated

Genes (Rattus norvegicus)
F2  (coagulation factor II, thrombin)

Genes (Mus musculus)
F2  (coagulation factor II)

Genes (Homo sapiens)
F2  (coagulation factor II, thrombin)


Additional Information