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Involvement of LPA1 receptor signaling in the reorganization of spinal input through Abeta-fibers in mice with partial sciatic nerve injury.

Xie W, Matsumoto M, Chun J, Ueda H - Mol Pain (2008)

Bottom Line: Lysophosphatidic acid receptor subtype LPA(1) is crucial for the initiation of neuropathic pain and underlying changes, such as up-regulation of Ca2+ channel alpha2delta-1 subunit in dorsal root ganglia (DRG), up-regulation of PKCgamma in the spinal dorsal horn, and demyelination of dorsal root fibers.Following nerve injury, the phosphorylation of extracellular-signal regulated kinase (pERK) by Abeta-fiber stimulation was observed in the superficial layer of spinal dorsal horn, where nociceptive C- or Adelta-fibers are innervated, but not in sham-operated wild-type mice.These results suggest that LPA(1) receptor-mediated signaling mechanisms also participate in functional cross-talk between Abeta- and C- or Adelta-fibers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8521, Japan. dm07182c@cc.nagasaki-u.ac.jp

ABSTRACT
Lysophosphatidic acid receptor subtype LPA(1) is crucial for the initiation of neuropathic pain and underlying changes, such as up-regulation of Ca2+ channel alpha2delta-1 subunit in dorsal root ganglia (DRG), up-regulation of PKCgamma in the spinal dorsal horn, and demyelination of dorsal root fibers. In the present study, we further examined the involvement of LPA(1) signaling in the reorganization of Abeta-fiber-mediated spinal transmission, which is presumed to underlie neuropathic allodynia. Following nerve injury, the phosphorylation of extracellular-signal regulated kinase (pERK) by Abeta-fiber stimulation was observed in the superficial layer of spinal dorsal horn, where nociceptive C- or Adelta-fibers are innervated, but not in sham-operated wild-type mice. However, the pERK signals were largely abolished in LPA(1) receptor knock-out (Lpar1-/-) mice, further supported by quantitative analyses of pERK-positive cells. These results suggest that LPA(1) receptor-mediated signaling mechanisms also participate in functional cross-talk between Abeta- and C- or Adelta-fibers.

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Lack of Aβ-fiber stimulation-induced ERK activation in Lpar1-/- mice after nerve injury. (A-H) Representative pictures of pERK signals in the ipsilateral spinal dorsal horn after the Aβ-fiber stimulation (2000 Hz) to the right hind paw (see Methods). Arrows in (D) indicate Aβ-fiber stimuli-specific pERK signals observed in wild-type nerve-injured mice. M: medial, L: lateral, D: dorsal, V: ventral. (I) Number of pERK-positive cells per section in ipsilateral dorsal horn. *:p < 0.05 vs. sham, #:p < 0.05 vs. wild-type (WT). Data represent the means ± S.E.M. from experiments using 4–6 mice.
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Figure 1: Lack of Aβ-fiber stimulation-induced ERK activation in Lpar1-/- mice after nerve injury. (A-H) Representative pictures of pERK signals in the ipsilateral spinal dorsal horn after the Aβ-fiber stimulation (2000 Hz) to the right hind paw (see Methods). Arrows in (D) indicate Aβ-fiber stimuli-specific pERK signals observed in wild-type nerve-injured mice. M: medial, L: lateral, D: dorsal, V: ventral. (I) Number of pERK-positive cells per section in ipsilateral dorsal horn. *:p < 0.05 vs. sham, #:p < 0.05 vs. wild-type (WT). Data represent the means ± S.E.M. from experiments using 4–6 mice.

Mentions: In sham-operated wild-type mice, no significant pERK signals were observed by the control treatment without electrical stimulation or by transcutaneous nerve stimuli for Aβ-fiber (2000 Hz, 1000 μA) in the L4–5 spinal dorsal horn (Fig. 1A, B). Although the nerve-injury alone did not induce pERK-signals (Fig, 1C), the Aβ-fiber-stimulation to the paw of nerve-injured mice induced pERK-positive signals in the ipsilateral superficial dorsal horn (laminae I-II), but not in the deeper regions of dorsal horn (lamina III-V) (Fig. 1D), as previously reported [8]. In the sham-operated Lpar1-/- mice, on the other hand, neither control treatment nor Aβ-fiber-stimulation induced any pERK signals (Fig. 1E, F). Although the nerve-injury alone also failed to induce pERK signals in Lpar1-/- mice, the Aβ-fiber-stimulation-induced pERK signals were largely abolished in nerve-injured Lpar1-/- mice (Fig. 1G, H). The number of pERK-positive cells in spinal dorsal horn was also increased in the nerve-injured wild-type mice after the Aβ-fiber stimuli, and this increase was significantly suppressed in Lpar1-/- mice (Fig. 1I).


Involvement of LPA1 receptor signaling in the reorganization of spinal input through Abeta-fibers in mice with partial sciatic nerve injury.

Xie W, Matsumoto M, Chun J, Ueda H - Mol Pain (2008)

Lack of Aβ-fiber stimulation-induced ERK activation in Lpar1-/- mice after nerve injury. (A-H) Representative pictures of pERK signals in the ipsilateral spinal dorsal horn after the Aβ-fiber stimulation (2000 Hz) to the right hind paw (see Methods). Arrows in (D) indicate Aβ-fiber stimuli-specific pERK signals observed in wild-type nerve-injured mice. M: medial, L: lateral, D: dorsal, V: ventral. (I) Number of pERK-positive cells per section in ipsilateral dorsal horn. *:p < 0.05 vs. sham, #:p < 0.05 vs. wild-type (WT). Data represent the means ± S.E.M. from experiments using 4–6 mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 1: Lack of Aβ-fiber stimulation-induced ERK activation in Lpar1-/- mice after nerve injury. (A-H) Representative pictures of pERK signals in the ipsilateral spinal dorsal horn after the Aβ-fiber stimulation (2000 Hz) to the right hind paw (see Methods). Arrows in (D) indicate Aβ-fiber stimuli-specific pERK signals observed in wild-type nerve-injured mice. M: medial, L: lateral, D: dorsal, V: ventral. (I) Number of pERK-positive cells per section in ipsilateral dorsal horn. *:p < 0.05 vs. sham, #:p < 0.05 vs. wild-type (WT). Data represent the means ± S.E.M. from experiments using 4–6 mice.
Mentions: In sham-operated wild-type mice, no significant pERK signals were observed by the control treatment without electrical stimulation or by transcutaneous nerve stimuli for Aβ-fiber (2000 Hz, 1000 μA) in the L4–5 spinal dorsal horn (Fig. 1A, B). Although the nerve-injury alone did not induce pERK-signals (Fig, 1C), the Aβ-fiber-stimulation to the paw of nerve-injured mice induced pERK-positive signals in the ipsilateral superficial dorsal horn (laminae I-II), but not in the deeper regions of dorsal horn (lamina III-V) (Fig. 1D), as previously reported [8]. In the sham-operated Lpar1-/- mice, on the other hand, neither control treatment nor Aβ-fiber-stimulation induced any pERK signals (Fig. 1E, F). Although the nerve-injury alone also failed to induce pERK signals in Lpar1-/- mice, the Aβ-fiber-stimulation-induced pERK signals were largely abolished in nerve-injured Lpar1-/- mice (Fig. 1G, H). The number of pERK-positive cells in spinal dorsal horn was also increased in the nerve-injured wild-type mice after the Aβ-fiber stimuli, and this increase was significantly suppressed in Lpar1-/- mice (Fig. 1I).

Bottom Line: Lysophosphatidic acid receptor subtype LPA(1) is crucial for the initiation of neuropathic pain and underlying changes, such as up-regulation of Ca2+ channel alpha2delta-1 subunit in dorsal root ganglia (DRG), up-regulation of PKCgamma in the spinal dorsal horn, and demyelination of dorsal root fibers.Following nerve injury, the phosphorylation of extracellular-signal regulated kinase (pERK) by Abeta-fiber stimulation was observed in the superficial layer of spinal dorsal horn, where nociceptive C- or Adelta-fibers are innervated, but not in sham-operated wild-type mice.These results suggest that LPA(1) receptor-mediated signaling mechanisms also participate in functional cross-talk between Abeta- and C- or Adelta-fibers.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8521, Japan. dm07182c@cc.nagasaki-u.ac.jp

ABSTRACT
Lysophosphatidic acid receptor subtype LPA(1) is crucial for the initiation of neuropathic pain and underlying changes, such as up-regulation of Ca2+ channel alpha2delta-1 subunit in dorsal root ganglia (DRG), up-regulation of PKCgamma in the spinal dorsal horn, and demyelination of dorsal root fibers. In the present study, we further examined the involvement of LPA(1) signaling in the reorganization of Abeta-fiber-mediated spinal transmission, which is presumed to underlie neuropathic allodynia. Following nerve injury, the phosphorylation of extracellular-signal regulated kinase (pERK) by Abeta-fiber stimulation was observed in the superficial layer of spinal dorsal horn, where nociceptive C- or Adelta-fibers are innervated, but not in sham-operated wild-type mice. However, the pERK signals were largely abolished in LPA(1) receptor knock-out (Lpar1-/-) mice, further supported by quantitative analyses of pERK-positive cells. These results suggest that LPA(1) receptor-mediated signaling mechanisms also participate in functional cross-talk between Abeta- and C- or Adelta-fibers.

Show MeSH
Related in: MedlinePlus