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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice
Published on: July 16, 2014
Temporal changes in spinal cord expression of mRNA for substance P, dynorphin and enkephalin in a model of chronic
G E Delander1, E Schött, E Brodin
1College of Pharmacy, Oregon State University, Corvallis 97331, USA.
Abstract:
We have used a partial sciatic nerve ligation model to examine the time course for changes in the expression of mRNA for three peptides related to pain transmission at spinal sites (dynorphin, enkephalin and substance P), during the development of allodynia. Enhanced expression of mRNA for dynorphin and substance P was observed in the dorsal horn on the same side as the partial nerve ligation. Increased expression of dynorphin mRNA was biphasic. The initial increases in expression of dynorphin mRNA occurred at 3 h, and a secondary peak was observed 1-3 days after surgery. The secondary increases coincided roughly with increased substance P mRNA expression. However, both dynorphin and substance P mRNA returned to control values after 1 week despite continuing allodynia. No significant changes in expression of mRNA for enkephalin were observed. The elevation of substance P mRNA in intrinsic spinal cord neurons may be secondary to changes in immediate early genes c-fos and jun-B, whereas the expression of dynorphin and enkephalin mRNA is differently regulated. The results also suggest that changes in the expression of the three neuropeptides are not critically involved in the development and maintenance of chronic pain or allodynia.
Insights
This study on nerve injury and pain found that while dynorphin and substance P mRNA levels change, they do not appear critical for chronic pain development or allodynia.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Pain transmission involves neuropeptides like dynorphin, enkephalin, and substance P in the spinal cord.
- Altered neuropeptide expression is implicated in the development of chronic pain conditions such as allodynia.
- Understanding the temporal dynamics of these neuropeptides is crucial for pain mechanism research.
Purpose of the Study:
- To investigate the time-dependent changes in spinal mRNA expression of dynorphin, enkephalin, and substance P during the development of allodynia.
- To determine the role of these neuropeptides in the establishment and maintenance of chronic pain states.
- To explore potential regulatory pathways involving immediate early genes.
Main Methods:
- Utilized a partial sciatic nerve ligation model in rodents to induce neuropathic pain and allodynia.
- Quantified changes in mRNA expression levels for dynorphin, enkephalin, and substance P in the dorsal horn using techniques like RT-PCR (not explicitly stated but implied).
- Monitored changes over various time points post-surgery, from hours to days.
Main Results:
- Observed transient, biphasic increases in dynorphin mRNA and increased substance P mRNA in the ipsilateral dorsal horn, coinciding with allodynia onset.
- Dynorphin mRNA showed an early peak at 3 hours and a secondary peak at 1-3 days post-ligation.
- Despite continuing allodynia, dynorphin and substance P mRNA levels returned to baseline within one week; enkephalin mRNA showed no significant changes.
Conclusions:
- The observed changes in dynorphin and substance P mRNA expression appear to be transient and not critically involved in the maintenance of chronic pain or allodynia.
- Neuropeptide regulation differs, with substance P potentially influenced by immediate early genes (c-fos, jun-B), while dynorphin and enkephalin exhibit distinct regulatory mechanisms.
- These findings suggest that other molecular mechanisms are primarily responsible for the development and persistence of neuropathic pain.
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