Cellular prion protein protects from inflammatory and neuropathic pain
<p>Abstract</p> <p>Cellular prion protein (PrP<sup>C</sup>) inhibits <it>N</it>-Methyl-<it>D</it>-Aspartate (NMDA) receptors. Since NMDA receptors play an important role in the transmission of pain signals in the dorsal horn of spinal cord, we th...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2011-08-01
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| Series: | Molecular Pain |
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| Online Access: | http://www.molecularpain.com/content/7/1/59 |
| _version_ | 1818640730705362944 |
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| author | Zamponi Gerald W Gadotti Vinicius M |
| author_facet | Zamponi Gerald W Gadotti Vinicius M |
| author_sort | Zamponi Gerald W |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Cellular prion protein (PrP<sup>C</sup>) inhibits <it>N</it>-Methyl-<it>D</it>-Aspartate (NMDA) receptors. Since NMDA receptors play an important role in the transmission of pain signals in the dorsal horn of spinal cord, we thus wanted to determine if PrP<sup>C </sup>null mice show a reduced threshold for various pain behaviours.</p> <p>We compared nociceptive thresholds between wild type and PrP<sup>C </sup>null mice in models of inflammatory and neuropathic pain, in the presence and the absence of a NMDA receptor antagonist. 2-3 months old male PrP<sup>C </sup>null mice exhibited an MK-801 sensitive decrease in the paw withdrawal threshold in response both mechanical and thermal stimuli. PrP<sup>C </sup>null mice also exhibited significantly longer licking/biting time during both the first and second phases of formalin-induced inflammation of the paw, which was again prevented by treatment of the mice with MK-801, and responded more strongly to glutamate injection into the paw. Compared to wild type animals, PrP<sup>C </sup>null mice also exhibited a significantly greater nociceptive response (licking/biting) after intrathecal injection of NMDA. Sciatic nerve ligation resulted in MK-801 sensitive neuropathic pain in wild-type mice, but did not further augment the basal increase in pain behaviour observed in the null mice, suggesting that mice lacking PrP<sup>C </sup>may already be in a state of tonic central sensitization. Altogether, our data indicate that PrP<sup>C </sup>exerts a critical role in modulating nociceptive transmission at the spinal cord level, and fit with the concept of NMDA receptor hyperfunction in the absence of PrP<sup>C</sup>.</p> |
| first_indexed | 2024-12-16T23:15:55Z |
| format | Article |
| id | doaj.art-b1508c380fb6433a90a9dcc8dcb3f08a |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-12-16T23:15:55Z |
| publishDate | 2011-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Pain |
| spelling | doaj.art-b1508c380fb6433a90a9dcc8dcb3f08a2022-12-21T22:12:18ZengSAGE PublishingMolecular Pain1744-80692011-08-01715910.1186/1744-8069-7-59Cellular prion protein protects from inflammatory and neuropathic painZamponi Gerald WGadotti Vinicius M<p>Abstract</p> <p>Cellular prion protein (PrP<sup>C</sup>) inhibits <it>N</it>-Methyl-<it>D</it>-Aspartate (NMDA) receptors. Since NMDA receptors play an important role in the transmission of pain signals in the dorsal horn of spinal cord, we thus wanted to determine if PrP<sup>C </sup>null mice show a reduced threshold for various pain behaviours.</p> <p>We compared nociceptive thresholds between wild type and PrP<sup>C </sup>null mice in models of inflammatory and neuropathic pain, in the presence and the absence of a NMDA receptor antagonist. 2-3 months old male PrP<sup>C </sup>null mice exhibited an MK-801 sensitive decrease in the paw withdrawal threshold in response both mechanical and thermal stimuli. PrP<sup>C </sup>null mice also exhibited significantly longer licking/biting time during both the first and second phases of formalin-induced inflammation of the paw, which was again prevented by treatment of the mice with MK-801, and responded more strongly to glutamate injection into the paw. Compared to wild type animals, PrP<sup>C </sup>null mice also exhibited a significantly greater nociceptive response (licking/biting) after intrathecal injection of NMDA. Sciatic nerve ligation resulted in MK-801 sensitive neuropathic pain in wild-type mice, but did not further augment the basal increase in pain behaviour observed in the null mice, suggesting that mice lacking PrP<sup>C </sup>may already be in a state of tonic central sensitization. Altogether, our data indicate that PrP<sup>C </sup>exerts a critical role in modulating nociceptive transmission at the spinal cord level, and fit with the concept of NMDA receptor hyperfunction in the absence of PrP<sup>C</sup>.</p>http://www.molecularpain.com/content/7/1/59Prion proteinpainknockout miceNMDA receptorspinal cord |
| spellingShingle | Zamponi Gerald W Gadotti Vinicius M Cellular prion protein protects from inflammatory and neuropathic pain Molecular Pain Prion protein pain knockout mice NMDA receptor spinal cord |
| title | Cellular prion protein protects from inflammatory and neuropathic pain |
| title_full | Cellular prion protein protects from inflammatory and neuropathic pain |
| title_fullStr | Cellular prion protein protects from inflammatory and neuropathic pain |
| title_full_unstemmed | Cellular prion protein protects from inflammatory and neuropathic pain |
| title_short | Cellular prion protein protects from inflammatory and neuropathic pain |
| title_sort | cellular prion protein protects from inflammatory and neuropathic pain |
| topic | Prion protein pain knockout mice NMDA receptor spinal cord |
| url | http://www.molecularpain.com/content/7/1/59 |
| work_keys_str_mv | AT zamponigeraldw cellularprionproteinprotectsfrominflammatoryandneuropathicpain AT gadottiviniciusm cellularprionproteinprotectsfrominflammatoryandneuropathicpain |