Abstract
The expression of NF-κB in the spinal cord is associated with neuropathic pain. However,
little is known about its expression beyond the spinal cord. Here we examined a spatial
and temporal pattern of the NF-κB expression in both spinal and supraspinal regions.
After chronic constriction injury (CCI) of the sciatic nerve, NF-κB (p65) expression
was significantly increased in the ipsilateral spinal cord. In contrast, the NF-κB
expression in the contralateral primary somatosensory cortex was decreased with no
significant differences seen in the thalamus. In the contralateral anterior cingulate
cortex, the NF-κB expression was increased significantly on day 14 as compared with
the sham group. In the contralateral amygdala, the NF-κB expression showed a time-dependent
downregulation after CCI, which became significant on day 14. MK-801 reduced nociceptive
behaviors and reversed the direction of NF-κB expression. These results indicate that
the CCI-induced expression of p65 NF-κB is both time-dependent and region-specific,
in areas that process both sensory-discriminative and motivational-affective dimensions
of pain.
Perspective
This article presents a spatiotemporal mapping of the NF-κB expression in spinal and
supraspinal regions after peripheral nerve injury. These findings point to an involvement
of NF-κB beyond the spinal cord in both the sensory discriminative and emotional affective
aspects of neuropathic pain processing.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Novel roles for the NF-kappaB signaling pathway in regulating neuronal function.Sci Signal. 2008; 1: pe7
- Immediate reorganization of the rat somatosensory thalamus after partial ligation of sciatic nerve.J Pain. 2001; 2: 220-228
- Pain perception: Is there a role for primary somatosensory cortex?.Proc Natl Acad Sci U S A. 1999; 96: 7705-7709
- NMDA antagonists and neuropathic pain: Multiple drug targets and multiple uses.Curr Pharm Des. 2005; 11: 2977-2994
- Neuropathic pain: A maladaptive response of the nervous system to damage.Annu Rev Neurosci. 2009; 32: 1-32
- Functional MRI of the brain detects neuropathic pain in experimental spinal cord injury.Pain. 2008; 138: 292-300
- Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.Nature. 1995; 375: 482-484
- Thalamic stimulation in neuropathic pain: 27 years later.Acta Neurol Belg. 2001; 101: 65-71
- A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia.Pain. 1988; 32: 77-88
- Evidence for a novel functional role of cannabinoid CB(2) receptors in the thalamus of neuropathic rats.Eur J Neurosci. 2008; 27: 1722-1730
- Central sensitization and LTP: Do pain and memory share similar mechanisms?.Trends Neurosci. 2003; 26: 696-705
- Constitutive NF-kappa B activity in neurons.Mol Cell Biol. 1994; 14: 3981-3992
- Selective contribution of Egr1 (zif/268) to persistent inflammatory pain.J Pain. 2005; 6: 12-20
- A brain-specific transcription activator.Neuron. 1989; 3: 563-572
- Chronic pain-induced astrocyte activation in the cingulate cortex with no change in neural or glial differentiation from neural stem cells in mice.Neurosci Lett. 2007; 415: 22-27
- GABAA but not GABAB receptors in the rostral anterior cingulate cortex selectively modulate pain-induced escape/avoidance behavior.Exp Neurol. 2007; 204: 182-194
- Differential effect of anterior cingulate cortex lesion on mechanical hypersensitivity and escape/avoidance behavior in an animal model of neuropathic pain.Exp Neurol. 2004; 188: 139-148
- Cytokine involvement in dynorphin-induced allodynia.Pain. 2000; 84: 159-167
- Liou H.-C. NF-κB/Rel Transcription Factor Family. Springer, New York, NY2006
- Increased activation of nuclear factor kappa B in rat lumbar dorsal root ganglion neurons following partial sciatic nerve injuries.Brain Res. 1998; 797: 243-254
- Patterns of increased brain activity indicative of pain in a rat model of peripheral mononeuropathy.J Neurosci. 1993; 13: 2689-2702
- Intrathecal MK-801 and local nerve anesthesia synergistically reduce nociceptive behaviors in rats with experimental peripheral mononeuropathy.Brain Res. 1992; 576: 254-262
- NF-kappaB in neuronal plasticity and neurodegenerative disorders.J Clin Invest. 2001; 107: 247-254
- NF-kappa B functions in synaptic signaling and behavior.Nat Neurosci. 2003; 6: 1072-1078
- Sensory, motivational, and central control determinants of pain.in: Kenshalo D. The Skin Senses. CC Thomas, Springfield1968: 423-439
- Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.Mol Ther. 2007; 15: 687-697
- Interleukin-1 activates transcription factor NF kappa B in glial cells.Biochem J. 1993; 294: 343-347
- Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction.J Neurochem. 2006; 97: 1369-1378
- Change in the expression of c-fos in the rat brain following sciatic nerve ligation.Neurosci Lett. 2003; 352: 231-233
- Neural plasticity after peripheral nerve injury and regeneration.Prog Neurobiol. 2007; 82: 163-201
- Forebrain pain mechanisms.Brain Res Rev. 2009; 60: 226-242
- The amygdala and persistent pain.Neuroscientist. 2004; 10: 221-234
- A crucial transcription factor for glial and neuronal cell function.Trends Neurosci. 1997; 20: 252-258
- Spinal nerve ligation-induced activation of nuclear factor kappaB is facilitated by prostaglandins in the affected spinal cord and is a critical step in the development of mechanical allodynia.Neuroscience. 2008; 155: 902-913
- Cortical modulation of pain.Cell Mol Life Sci. 2005; 62: 44-52
- Deep brain stimulation for the alleviation of post-stroke neuropathic pain.Pain. 2006; 120: 202-206
- Paxinos G. Watson C. The Rat Brain in Stereotaxic Coordinates. 4th ed. Academic Press, San Diego, CA1998
- Amygdala GABA-A receptor involvement in mediating sensory-discriminative and affective-motivational pain responses in a rat model of peripheral nerve injury.Pain. 2007; 127: 17-26
- Theories of pain.in: Mao J. Translational Pain Research. Vol. I. Nova Science Publishers, New York2006: 1-27
- Nociceptive behavior in animal models for peripheral neuropathy: Spinal and supraspinal mechanisms.Prog Neurobiol. 2008; 86: 22-47
- NF-kappa B decoy suppresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model.Neuroreport. 2001; 12: 2079-2084
- Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury.J Neurosci. 2005; 25: 7317-7323
- Short-term synaptic plasticity in the nociceptive thalamic-anterior cingulate pathway.Mol Pain. 2009; 5: 51
- Cytokine regulation of interleukin-6 gene expression in astrocytes involves activation of an NF-kappa B-like nuclear protein.J Neuroimmunol. 1992; 39: 231-242
- Analgesic effect of milnacipran is associated with c-Fos expression in the anterior cingulate cortex in the rat neuropathic pain model.Neurosci Res. 2009; 64: 380-384
- Extra-territorial pain in rats with a peripheral mononeuropathy: Mechano-hyperalgesia and mechano-allodynia in the territory of an uninjured nerve.Pain. 1994; 57: 375-382
- Genetic elimination of behavioral sensitization in mice lacking calmodulin-stimulated adenylyl cyclases.Neuron. 2002; 36: 713-726
- Genetic enhancement of inflammatory pain by forebrain NR2B overexpression.Nat Neurosci. 2001; 4: 164-169
- Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury.Pain. 2009; 141: 52-59
- Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation.J Neurosci. 2005; 25: 11107-11116
- Cerebral cortex modulation of pain.Acta Pharmacol Sin. 2009; 30: 31-41
- Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex.J Neurosci. 2008; 28: 7445-7453
- Molecular mechanisms of pain in the anterior cingulate cortex.J Neurosci Res. 2006; 84: 927-933
Article Info
Publication History
Published online: May 31, 2010
Accepted:
March 24,
2010
Received in revised form:
March 2,
2010
Received:
February 3,
2010
Footnotes
Supported by NIH RO1 grants DE18214, DE18538 , and NS45681 .
The authors claim no conflict of interest.
Identification
Copyright
© 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
