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Peripheral mechanisms of neuropathic pain - involvement of lysophosphatidic acid receptor-mediated demyelination.

Ueda H - Mol Pain (2008)

Bottom Line: These changes, or plasticity, might underlie unique neuropathic pain-specific phenotype modifications - decreased unmyelinated-fiber functions, but increased myelinated A-fiber functions.Throughout a series of studies, using novel nociceptive tests to characterize sensory-fiber or pain modality-specific nociceptive behaviors, it was demonstrated that communication between innocuous and noxious sensory fibers might play a role in allodynia mechanisms.These results lead to further hypotheses of physical communication between innocuous Abeta- and noxious C- or Adelta-fibers to influence the molecular mechanisms of allodynia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. ueda@nagasaki-u.ac.jp

ABSTRACT
Recent advances in pain research provide a clear picture for the molecular mechanisms of acute pain; substantial information concerning plasticity that occurs during neuropathic pain has also become available. The peripheral mechanisms responsible for neuropathic pain are found in the altered gene/protein expression of primary sensory neurons. With damage to peripheral sensory fibers, a variety of changes in pain-related gene expression take place in dorsal root ganglion neurons. These changes, or plasticity, might underlie unique neuropathic pain-specific phenotype modifications - decreased unmyelinated-fiber functions, but increased myelinated A-fiber functions. Another characteristic change is observed in allodynia, the functional change of tactile to nociceptive perception. Throughout a series of studies, using novel nociceptive tests to characterize sensory-fiber or pain modality-specific nociceptive behaviors, it was demonstrated that communication between innocuous and noxious sensory fibers might play a role in allodynia mechanisms. Because neuropathic pain in peripheral and central demyelinating diseases develops as a result of aberrant myelination in experimental animals, demyelination seems to be a key mechanism of plasticity in neuropathic pain. More recently, we discovered that lysophosphatidic acid receptor activation initiates neuropathic pain, as well as possible peripheral mechanism of demyelination after nerve injury. These results lead to further hypotheses of physical communication between innocuous Abeta- and noxious C- or Adelta-fibers to influence the molecular mechanisms of allodynia.

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Related in: MedlinePlus

LPA-induced demyelination of dorsal root fibers in ex vivo culture experiments [74]. The addition of LPA (100 nM) causes demyelination of acutely isolated dorsal root fibers after 12 h, in both scanning and transmission electron microscope (SEM and TEM) analyses. LPA also causes morphological changes in Schwann cells of the Ramaak bundle, which induce close membrane apposition.
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Figure 2: LPA-induced demyelination of dorsal root fibers in ex vivo culture experiments [74]. The addition of LPA (100 nM) causes demyelination of acutely isolated dorsal root fibers after 12 h, in both scanning and transmission electron microscope (SEM and TEM) analyses. LPA also causes morphological changes in Schwann cells of the Ramaak bundle, which induce close membrane apposition.

Mentions: Consistent with the fact that receptor-mediated LPA signaling influences the morphology of Schwann cells [70], the i.t. injection of LPA (1 nmol), as well as partial sciatic nerve injury, caused demyelination of the dorsal root within 24 h; this demyelination was abolished by pretreating with BoTN/C3 [73]. An ex vivo study using dorsal root fibers also demonstrated that the addition of LPA causes demyelination of A-fibers and damage to Schwann cells, which promotes direct contact between C fibers in the Remak bundle [74] (Fig. 2). LPA-induced demyelination was, however, reversed by BoTN/C3 or Y27632, a ROCK inhibitor. In addition, myelin basic protein (MBP) and myelin protein zero (MP0) were down-regulated. LPA-injection (i.t.) or partial sciatic nerve injury in mice produced demyelination in the dorsal root, but not in the spinal nerve, although the addition of LPA led to significant demyelination in both fibers ex vivo, which suggests that in vivo demyelination occurs specifically at the dorsal-root, proximal to the spinal cord. Furthermore, we observed that simultaneous ligation of the residual half of the sciatic nerve triggered only a slight increase in demyelination. Taken together, these findings provide speculation to the theory that certain spinal cord-originating extracellular signaling molecules, including LPA, diffuse to the dorsal root to cause demyelination.


Peripheral mechanisms of neuropathic pain - involvement of lysophosphatidic acid receptor-mediated demyelination.

Ueda H - Mol Pain (2008)

LPA-induced demyelination of dorsal root fibers in ex vivo culture experiments [74]. The addition of LPA (100 nM) causes demyelination of acutely isolated dorsal root fibers after 12 h, in both scanning and transmission electron microscope (SEM and TEM) analyses. LPA also causes morphological changes in Schwann cells of the Ramaak bundle, which induce close membrane apposition.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2365930&req=5

Figure 2: LPA-induced demyelination of dorsal root fibers in ex vivo culture experiments [74]. The addition of LPA (100 nM) causes demyelination of acutely isolated dorsal root fibers after 12 h, in both scanning and transmission electron microscope (SEM and TEM) analyses. LPA also causes morphological changes in Schwann cells of the Ramaak bundle, which induce close membrane apposition.
Mentions: Consistent with the fact that receptor-mediated LPA signaling influences the morphology of Schwann cells [70], the i.t. injection of LPA (1 nmol), as well as partial sciatic nerve injury, caused demyelination of the dorsal root within 24 h; this demyelination was abolished by pretreating with BoTN/C3 [73]. An ex vivo study using dorsal root fibers also demonstrated that the addition of LPA causes demyelination of A-fibers and damage to Schwann cells, which promotes direct contact between C fibers in the Remak bundle [74] (Fig. 2). LPA-induced demyelination was, however, reversed by BoTN/C3 or Y27632, a ROCK inhibitor. In addition, myelin basic protein (MBP) and myelin protein zero (MP0) were down-regulated. LPA-injection (i.t.) or partial sciatic nerve injury in mice produced demyelination in the dorsal root, but not in the spinal nerve, although the addition of LPA led to significant demyelination in both fibers ex vivo, which suggests that in vivo demyelination occurs specifically at the dorsal-root, proximal to the spinal cord. Furthermore, we observed that simultaneous ligation of the residual half of the sciatic nerve triggered only a slight increase in demyelination. Taken together, these findings provide speculation to the theory that certain spinal cord-originating extracellular signaling molecules, including LPA, diffuse to the dorsal root to cause demyelination.

Bottom Line: These changes, or plasticity, might underlie unique neuropathic pain-specific phenotype modifications - decreased unmyelinated-fiber functions, but increased myelinated A-fiber functions.Throughout a series of studies, using novel nociceptive tests to characterize sensory-fiber or pain modality-specific nociceptive behaviors, it was demonstrated that communication between innocuous and noxious sensory fibers might play a role in allodynia mechanisms.These results lead to further hypotheses of physical communication between innocuous Abeta- and noxious C- or Adelta-fibers to influence the molecular mechanisms of allodynia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. ueda@nagasaki-u.ac.jp

ABSTRACT
Recent advances in pain research provide a clear picture for the molecular mechanisms of acute pain; substantial information concerning plasticity that occurs during neuropathic pain has also become available. The peripheral mechanisms responsible for neuropathic pain are found in the altered gene/protein expression of primary sensory neurons. With damage to peripheral sensory fibers, a variety of changes in pain-related gene expression take place in dorsal root ganglion neurons. These changes, or plasticity, might underlie unique neuropathic pain-specific phenotype modifications - decreased unmyelinated-fiber functions, but increased myelinated A-fiber functions. Another characteristic change is observed in allodynia, the functional change of tactile to nociceptive perception. Throughout a series of studies, using novel nociceptive tests to characterize sensory-fiber or pain modality-specific nociceptive behaviors, it was demonstrated that communication between innocuous and noxious sensory fibers might play a role in allodynia mechanisms. Because neuropathic pain in peripheral and central demyelinating diseases develops as a result of aberrant myelination in experimental animals, demyelination seems to be a key mechanism of plasticity in neuropathic pain. More recently, we discovered that lysophosphatidic acid receptor activation initiates neuropathic pain, as well as possible peripheral mechanism of demyelination after nerve injury. These results lead to further hypotheses of physical communication between innocuous Abeta- and noxious C- or Adelta-fibers to influence the molecular mechanisms of allodynia.

Show MeSH
Related in: MedlinePlus