The preprota
chykinin A gene (ppt-A)
codes for Substan
ce P (SP), supports no
ci
ceptive sensitization, and modulates inflammatory responses after in
cision. Repeated opioid use produ
ces paradoxi
cal pain sensitization¡ªtermed opioid-indu
ced hyperalgesia (OIH) ¡ªwhi
ch
can exa
cerbate pain after in
cision. Here the
contribution of SP to peri-in
cisional no
ci
ceptive sensitization and no
ci
ceptive mediator produ
ction after opioid treatment was examined utilizing ppt-A kno
ckout (?/?) mi
ce and the neurokinin (NK1) re
ceptor antagonist LY303870. Less me
chani
cal allodynia was observed in ppt
-A
?/? mi
ce
compared to wild types (wt) after morphine treatment both before and after in
cision. Moreover, LY303870 administered with morphine redu
ced in
cisional hyperalgesia in wt mi
ce. In
cision after saline or es
calating morphine treatment upregulated skin IL-1¦Â, IL-6, G-CSF and MIP-1¦Á levels in ppt-A
?/? and wt mi
ce similarly. However,
chroni
c morphine treatment greatly exa
cerbated in
creases in skin nerve growth fa
ctor levels after in
cision, an effe
ct entirely dependent upon inta
ct SP signaling. Additionally, SP dependent upregulation of prodynorphin, NMDA1 and NK1 re
ceptor expression in spinal
cord was seen after morphine treatment and in
cision. A similar pattern was seen for 5-HT3 re
ceptor expression in tissue from dorsal root ganglia. Therefore, SP may work at both
central and peripheral sites to enhan
ce no
ci
ceptive sensitization after morphine treatment and in
cision.
class=""h4"">Perspective
These studies show that SP signaling modulates enhanced nerve growth factor production and changes in neuronal gene expression seen after incision in mice previously exposed to morphine.