Abstract
We examined the pharmacologic characteristics of herpes simplex virus (HSV) vector-mediated expression of proenkephalin in the dorsal root ganglion in a rodent model of neuropathic pain. We found that: (i) vector-mediated enkephalin produced an antiallodynic effect that was reversed by naloxone; (ii) vector-mediated enkephalin production in animals with spinal nerve ligation prevented the induction of c-fos expression in second order sensory neurons in the dorsal horn of spinal cord; (iii) the effect of vector-mediated enkephalin enhanced the effect of morphine, reducing the ED50 of morphine 10-fold; (iv) animals did not develop tolerance to the continued production of vector-mediated enkephalin over a period of several weeks; and, (v) vector transduction continued to provide an analgesic effect despite the induction of tolerance to morphine. This is the first demonstration of gene transfer to provide an analgesic effect in neuropathic pain. The pharmacologic analysis demonstrates that transgene-mediated expression and local release of opioid peptides produce some effects that are distinct from peptide analogues delivered pharmacologically.
| Original language | English |
|---|---|
| Pages (from-to) | 135-142 |
| Number of pages | 8 |
| Journal | Pain |
| Volume | 102 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Mar 1 2003 |
| Externally published | Yes |
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Keywords
- Gene transfer
- Herpes simplex virus
- Morphine
- Pain
- Tolerance
ASJC Scopus subject areas
- Clinical Neurology
- Psychiatry and Mental health
- Neurology
- Neuroscience(all)
- Pharmacology
- Clinical Psychology
Cite this
Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain. / Hao, Shuanglin; Mata, Marina; Goins, William; Glorioso, Joseph C.; Fink, David J.
In: Pain, Vol. 102, No. 1-2, 01.03.2003, p. 135-142.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transgene-mediated enkephalin release enhances the effect of morphine and evades tolerance to produce a sustained antiallodynic effect in neuropathic pain
AU - Hao, Shuanglin
AU - Mata, Marina
AU - Goins, William
AU - Glorioso, Joseph C.
AU - Fink, David J.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - We examined the pharmacologic characteristics of herpes simplex virus (HSV) vector-mediated expression of proenkephalin in the dorsal root ganglion in a rodent model of neuropathic pain. We found that: (i) vector-mediated enkephalin produced an antiallodynic effect that was reversed by naloxone; (ii) vector-mediated enkephalin production in animals with spinal nerve ligation prevented the induction of c-fos expression in second order sensory neurons in the dorsal horn of spinal cord; (iii) the effect of vector-mediated enkephalin enhanced the effect of morphine, reducing the ED50 of morphine 10-fold; (iv) animals did not develop tolerance to the continued production of vector-mediated enkephalin over a period of several weeks; and, (v) vector transduction continued to provide an analgesic effect despite the induction of tolerance to morphine. This is the first demonstration of gene transfer to provide an analgesic effect in neuropathic pain. The pharmacologic analysis demonstrates that transgene-mediated expression and local release of opioid peptides produce some effects that are distinct from peptide analogues delivered pharmacologically.
AB - We examined the pharmacologic characteristics of herpes simplex virus (HSV) vector-mediated expression of proenkephalin in the dorsal root ganglion in a rodent model of neuropathic pain. We found that: (i) vector-mediated enkephalin produced an antiallodynic effect that was reversed by naloxone; (ii) vector-mediated enkephalin production in animals with spinal nerve ligation prevented the induction of c-fos expression in second order sensory neurons in the dorsal horn of spinal cord; (iii) the effect of vector-mediated enkephalin enhanced the effect of morphine, reducing the ED50 of morphine 10-fold; (iv) animals did not develop tolerance to the continued production of vector-mediated enkephalin over a period of several weeks; and, (v) vector transduction continued to provide an analgesic effect despite the induction of tolerance to morphine. This is the first demonstration of gene transfer to provide an analgesic effect in neuropathic pain. The pharmacologic analysis demonstrates that transgene-mediated expression and local release of opioid peptides produce some effects that are distinct from peptide analogues delivered pharmacologically.
KW - Gene transfer
KW - Herpes simplex virus
KW - Morphine
KW - Pain
KW - Tolerance
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UR - http://www.scopus.com/inward/citedby.url?scp=0037333714&partnerID=8YFLogxK
U2 - 10.1016/s0304-3959(02)00346-9
DO - 10.1016/s0304-3959(02)00346-9
M3 - Article
C2 - 12620604
AN - SCOPUS:0037333714
VL - 102
SP - 135
EP - 142
JO - Pain
JF - Pain
SN - 0304-3959
IS - 1-2
ER -