PMID- 16775210
OWN - NLM
STAT- MEDLINE
DCOM- 20061206
LR  - 20220410
IS  - 0022-3077 (Print)
IS  - 0022-3077 (Linking)
VI  - 96
IP  - 5
DP  - 2006 Nov
TI  - MCP-1 enhances excitability of nociceptive neurons in chronically compressed 
      dorsal root ganglia.
PG  - 2189-99
AB  - Previous experimental results from our laboratory demonstrated that monocyte 
      chemoattractant protein-1 (MCP-1) depolarizes or increases the excitability of 
      nociceptive neurons in the intact dorsal root ganglion (DRG) after a chronic 
      compression of the DRG (CCD), an injury that upregulates neuronal expression of 
      both MCP-1 and mRNA for its receptor CCR2. We presently explore the ionic 
      mechanisms underlying the excitatory effects of MCP-1. MCP-1 (100 nM) was 
      applied, after CCD, to acutely dissociated small DRG neurons with nociceptive 
      properties. Under current clamp, the proportion of neurons depolarized was 
      similar to that previously observed for CCD-treated neurons in the intact 
      ganglion, although the magnitude of depolarization was greater. MCP-1 induced a 
      decrease in rheobase by 44 +/- 10% and some cells became spontaneously active at 
      resting potential. Action potential width at a voltage equal to 10% of the peak 
      height was increased from 4.94 +/- 0.23 to 5.90 +/- 0.47 ms. In voltage clamp, 
      MCP-1 induced an inward current in 27 of 50 neurons held at -60 mV, which 
      increased with concentration over the range of 3 to 300 nM (EC(50) = 45 nM). The 
      MCP-1-induced current was not voltage dependent and had an estimated reversal 
      potential of -27 mV. In addition, MCP-1 inhibited a voltage-dependent, 
      noninactivating outward current, presumably a delayed rectifier type K(+) 
      conductance. We conclude that MCP-1 enhances excitability in CCD neurons by, at 
      least, two mechanisms: 1) activation of a nonvoltage-dependent depolarizing 
      current with characteristics similar to a nonselective cation conductance and 2) 
      inhibition of a voltage-dependent outward current.
FAU - Sun, J H
AU  - Sun JH
AD  - Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 
      06510, USA.
FAU - Yang, B
AU  - Yang B
FAU - Donnelly, D F
AU  - Donnelly DF
FAU - Ma, C
AU  - Ma C
FAU - LaMotte, R H
AU  - LaMotte RH
LA  - eng
GR  - NS-14624/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060614
PL  - United States
TA  - J Neurophysiol
JT  - Journal of neurophysiology
JID - 0375404
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Potassium Channels)
SB  - IM
CIN - J Neurophysiol. 2006 Nov;96(5):2171-2. PMID: 16807343
MH  - Action Potentials/drug effects
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/*pharmacology
MH  - Chronic Disease
MH  - Female
MH  - Ganglia, Spinal/*physiopathology
MH  - Membrane Potentials/drug effects
MH  - Neurons, Afferent/*drug effects
MH  - Nociceptors/*drug effects
MH  - Pain/*physiopathology
MH  - Patch-Clamp Techniques
MH  - Potassium Channels/drug effects
MH  - Radiculopathy/*physiopathology
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2006/06/16 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/06/16 09:00
PHST- 2006/06/16 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/06/16 09:00 [entrez]
AID - 00222.2006 [pii]
AID - 10.1152/jn.00222.2006 [doi]
PST - ppublish
SO  - J Neurophysiol. 2006 Nov;96(5):2189-99. doi: 10.1152/jn.00222.2006. Epub 2006 Jun 
      14.