Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients.
Glial activation via Toll-like receptor (TLR) signaling has been shown in animals to play an important role in the initiation and establishment of chronic pain. However, our ability to assess this central immune reactivity in clinical pain populations is currently lacking. Peripheral blood mononucle...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3429430?pdf=render |
| _version_ | 1828866089034973184 |
|---|---|
| author | Yuen H Kwok Mark R Hutchinson Melanie G Gentgall Paul E Rolan |
| author_facet | Yuen H Kwok Mark R Hutchinson Melanie G Gentgall Paul E Rolan |
| author_sort | Yuen H Kwok |
| collection | DOAJ |
| description | Glial activation via Toll-like receptor (TLR) signaling has been shown in animals to play an important role in the initiation and establishment of chronic pain. However, our ability to assess this central immune reactivity in clinical pain populations is currently lacking. Peripheral blood mononuclear cells (PBMCs) are an accessible source of TLR expressing cells that may mirror similarities in TLR responsiveness of the central nervous system. The aim of this study was to characterize the IL-1β response to various TLR agonists in isolated PBMCs from chronic pain sufferers (on and not on opioids) and pain-free controls. Venous blood was collected from 11 chronic pain sufferers on opioids (≥ 20 mg of morphine / day), 8 chronic pain sufferers not on opioids and 11 pain-free controls. PBMCs were isolated and stimulated in vitro with a TLR2 (Pam3CSK4), TLR4 (LPS) or TLR7 (imiquimod) agonist. IL-1β released into the supernatant was measured with ELISA. Significantly increased IL-1β expression was found in PBMCs from chronic pain sufferers (on and not on opioids) compared with pain-free controls for TLR2 (F((6, 277)) = 15, P<0.0001), TLR4 (F((8, 263)) = 3, P = 0.002) and TLR7 (F((2,201)) = 5, P = 0.005) agonists. These data demonstrate that PBMCs from chronic pain sufferers were more responsive to TLR agonists compared with controls, suggesting peripheral cells may have the potential to become a source of biomarkers for chronic pain. |
| first_indexed | 2024-12-13T04:43:07Z |
| format | Article |
| id | doaj.art-ac297bfff59247b4a8936f602a5fd398 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T04:43:07Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ac297bfff59247b4a8936f602a5fd3982022-12-21T23:59:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4423210.1371/journal.pone.0044232Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients.Yuen H KwokMark R HutchinsonMelanie G GentgallPaul E RolanGlial activation via Toll-like receptor (TLR) signaling has been shown in animals to play an important role in the initiation and establishment of chronic pain. However, our ability to assess this central immune reactivity in clinical pain populations is currently lacking. Peripheral blood mononuclear cells (PBMCs) are an accessible source of TLR expressing cells that may mirror similarities in TLR responsiveness of the central nervous system. The aim of this study was to characterize the IL-1β response to various TLR agonists in isolated PBMCs from chronic pain sufferers (on and not on opioids) and pain-free controls. Venous blood was collected from 11 chronic pain sufferers on opioids (≥ 20 mg of morphine / day), 8 chronic pain sufferers not on opioids and 11 pain-free controls. PBMCs were isolated and stimulated in vitro with a TLR2 (Pam3CSK4), TLR4 (LPS) or TLR7 (imiquimod) agonist. IL-1β released into the supernatant was measured with ELISA. Significantly increased IL-1β expression was found in PBMCs from chronic pain sufferers (on and not on opioids) compared with pain-free controls for TLR2 (F((6, 277)) = 15, P<0.0001), TLR4 (F((8, 263)) = 3, P = 0.002) and TLR7 (F((2,201)) = 5, P = 0.005) agonists. These data demonstrate that PBMCs from chronic pain sufferers were more responsive to TLR agonists compared with controls, suggesting peripheral cells may have the potential to become a source of biomarkers for chronic pain.http://europepmc.org/articles/PMC3429430?pdf=render |
| spellingShingle | Yuen H Kwok Mark R Hutchinson Melanie G Gentgall Paul E Rolan Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients. PLoS ONE |
| title | Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients. |
| title_full | Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients. |
| title_fullStr | Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients. |
| title_full_unstemmed | Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients. |
| title_short | Increased responsiveness of peripheral blood mononuclear cells to in vitro TLR 2, 4 and 7 ligand stimulation in chronic pain patients. |
| title_sort | increased responsiveness of peripheral blood mononuclear cells to in vitro tlr 2 4 and 7 ligand stimulation in chronic pain patients |
| url | http://europepmc.org/articles/PMC3429430?pdf=render |
| work_keys_str_mv | AT yuenhkwok increasedresponsivenessofperipheralbloodmononuclearcellstoinvitrotlr24and7ligandstimulationinchronicpainpatients AT markrhutchinson increasedresponsivenessofperipheralbloodmononuclearcellstoinvitrotlr24and7ligandstimulationinchronicpainpatients AT melanieggentgall increasedresponsivenessofperipheralbloodmononuclearcellstoinvitrotlr24and7ligandstimulationinchronicpainpatients AT paulerolan increasedresponsivenessofperipheralbloodmononuclearcellstoinvitrotlr24and7ligandstimulationinchronicpainpatients |