A Novel Method to Quantify Histochemical Changes Throughout the Mediolateral Axis of the Substantia Gelatinosa After Spared Nerve Injury: Characterization with TRPV1 and Substance P

Corder, Gregory; Siegel, Andrew L.; Intondi, A.; Zhang, Xing; Zadina, James E.; Taylor, Bradley K.

doi:10.1016/j.jpain.2009.09.008

Cited by 25 publications

(25 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results are consistent with a report that SNI did not reduce the expression of TRPV1 immunoreactivity within the territory innervated by the uninjured sural nerve in the spinal dorsal horn (31). From these results, it is considered that normal thermal sensitivity was maintained because of sparing of TRPV1-positive fibers in this SNI model.…”

Section: Discussionsupporting

confidence: 92%

Contribution of TRPV1 Receptor^|^ndash;Expressing Fibers to Spinal Ventral Root After-Discharges and Mechanical Hyperalgesia in a Spared Nerve Injury (SNI) Rat Model

2013

View full text Add to dashboard Cite

Abstract. Neuropathic pain induces allodynia and hyperalgesia. In the spared nerve injury (SNI) model, marked mechanical hyperalgesia is manifested as prolongation of the duration of paw withdrawal after pin stimulation. We have previously reported that spinal ventral root discharges (after-discharges) after cessation of noxious mechanical stimulation applied to the corresponding hindpaw were prolonged in anesthetized spinalized rats. Since these after-discharges occurred through transient receptor potential (TRP) V1-positive fibers, these fibers could contribute to mechanical hyperalgesia. Therefore, we examined whether selective deletion of TRPV1-positive fibers by resiniferatoxin, an ultrapotent TRPV1 agonist, would affect the behavioral changes and ventral root discharges in SNI rats. Mechanical allodynia in the von Frey test, mechanical hyperalgesia after pin stimulation, and enhancement of ventral root discharges, but not thermal hyperalgesia in the plantar test, appeared in Wistar rats with SNI. Mechanical hyperalgesia was abolished by treatment with resiniferatoxin, whereas mechanical allodynia was not affected. Moreover, resiniferatoxin eliminated after-discharges completely. These results show that TRPV1-positive fibers do not participate in the mechanical allodynia caused by sensitization of Aβ-fibers, but contribute to the enhancement of after-discharges and mechanical hyperalgesia following SNI. It is suggested that the mechanisms responsible for generating mechanical allodynia differ from those for prolongation of mechanical hyperalgesia.

show abstract

Section: Discussionsupporting

confidence: 92%

Contribution of TRPV1 Receptor^|^ndash;Expressing Fibers to Spinal Ventral Root After-Discharges and Mechanical Hyperalgesia in a Spared Nerve Injury (SNI) Rat Model

2013

View full text Add to dashboard Cite

show abstract

“…Investigations of nerve injury-induced activation of astrocytes in areas of the dorsal horn innervated by injured versus uninjured afferents are sparse [4;15;94]. Here, our immunohistochemical quantification method [15] revealed that nerve injury increased GFAP expression in regions of the ipsilateral dorsal horn innervated by both injured tibial afferents (medial) and uninjured sural afferents (lateral).…”

Section: Discussionmentioning

confidence: 94%

“…Here, our immunohistochemical quantification method [15] revealed that nerve injury increased GFAP expression in regions of the ipsilateral dorsal horn innervated by both injured tibial afferents (medial) and uninjured sural afferents (lateral). This is consistent with qualitative studies showing that astrocyte activation extends beyond injured territories [4], and suggests that astrocytes induce hyperalgesia by sensitizing intact nociceptive pathways.…”

Section: Discussionmentioning

confidence: 99%

“…In SNI studies the dorsal horn was separated into lamina I-II, lamina III-IV, and lamina V as well as medial, central, and lateral regions of interest (ROI). Medial-lateral ROI correspond to afferent input from the tibial (medial), common peroneal (central), and sural (lateral) receptive fields as previously described [15]. Each of the six ROI were quantified and analyzed separately.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Pioglitazone rapidly reduces neuropathic pain through astrocyte and nongenomic PPARγ mechanisms

Griggs

Donahue

Morgenweck

et al. 2015

Pain

Self Cite

View full text Add to dashboard Cite

Repeated administration of peroxisome proliferator-activated receptor gamma (PPARγ) agonists reduces neuropathic pain-like behavior and associated changes in glial activation in the spinal cord dorsal horn. As PPARγ is a nuclear receptor, sustained changes in gene expression are widely believed to be the mechanism of pain reduction. However, we recently reported that a single intrathecal injection of pioglitazone, a PPARγ agonist, reduced hyperalgesia within 30 minutes, a time frame that is typically less than that required for genomic mechanisms. To determine the very rapid anti-hyperalgesic actions of PPARγ activation we administered pioglitazone to rats with spared nerve injury (SNI) and evaluated hyperalgesia. Pioglitazone inhibited hyperalgesia within 5 min of injection, consistent with a non-genomic mechanism. Systemic or intrathecal administration of GW9662, a PPARγ antagonist, inhibited the anti-hyperalgesic actions of intraperitoneal or intrathecal pioglitazone, suggesting a spinal PPARγ-dependent mechanism. To further address the contribution of non-genomic mechanisms, we blocked new protein synthesis in the spinal cord with anisomycin. When co-administered intrathecally, anisomycin did not change pioglitazone anti-hyperalgesia at an early 7.5 min timepoint, further supporting a rapid non-genomic mechanism. At later timepoints anisomycin reduced pioglitazone anti-hyperalgesia, suggesting a delayed recruitment of genomic mechanisms. Pioglitazone reduction of SNI-induced increases in GFAP expression occurred more rapidly than expected, within 60 min. We are the first to show that activation of spinal PPARγ rapidly reduces neuropathic pain independent from canonical genomic activity. We conclude that acute pioglitazone inhibits neuropathic pain in part by reducing astrocyte activation, and via both genomic and non-genomic PPARγ mechanisms.

show abstract

“…We focused our quantification of the number of pERK immunopositive cell profiles within lamina I-II, where the majority of C-fibers and nociceptive peripheral afferents terminate within the dorsal horn 4, 14 . Colabeling of pERK with NeuN is expressed as the percentage of the total number of pERK profiles in laminae I-II also expressing NeuN.…”

Section: Methodsmentioning

confidence: 99%

Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

Griggs

Donahue

Adkins

et al. 2016

The Journal of Pain

Self Cite

View full text Add to dashboard Cite

Thiazolidinedione drugs (TZDs) such as pioglitazone are FDA-approved for the treatment of insulin resistance in type 2 diabetes. However, whether TZDs reduce painful diabetic neuropathy (PDN) remains unknown. Therefore we tested the hypothesis that chronic administration of pioglitazone would reduce PDN in Zucker Diabetic Fatty (ZDFfa/fa) rats. Compared to Zucker Lean (ZLfa/+) controls, ZDF developed: (1) elevated blood glucose, HbA1c, methylglyoxal and insulin; (2) mechanical and thermal hyperalgesia at the hindpaw; (3) increased avoidance of noxious mechanical probes in a mechanical conflict avoidance behavioral assay, the first report of a measure of affective-motivational pain-like behavior in ZDF; and (4) exaggerated lumbar dorsal horn immunohistochemical expression of pressure-evoked phosphorylated extracellular signal-regulated kinase (pERK). Seven weeks of pioglitazone (30 mg · kg−1 · d−1 in food) reduced blood glucose, HbA1c, hyperalgesia, and pERK expression in ZDF. This is the first report to reveal hyperalgesia and spinal sensitization in the same ZDF animals, both evoked by a noxious mechanical stimulus that reflects pressure pain frequently associated with clinical PDN. As pioglitazone provides the combined benefit of reducing hyperglycemia, hyperalgesia, and central sensitization, we suggest that TZDs represent an attractive pharmacotherapy in patients with type 2 diabetes-associated pain.

show abstract

A Novel Method to Quantify Histochemical Changes Throughout the Mediolateral Axis of the Substantia Gelatinosa After Spared Nerve Injury: Characterization with TRPV1 and Substance P

Cited by 25 publications

References 37 publications

Contribution of TRPV1 Receptor^|^ndash;Expressing Fibers to Spinal Ventral Root After-Discharges and Mechanical Hyperalgesia in a Spared Nerve Injury (SNI) Rat Model

Contribution of TRPV1 Receptor^|^ndash;Expressing Fibers to Spinal Ventral Root After-Discharges and Mechanical Hyperalgesia in a Spared Nerve Injury (SNI) Rat Model

Pioglitazone rapidly reduces neuropathic pain through astrocyte and nongenomic PPARγ mechanisms

Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

Contact Info

Product

Resources

About