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Effects of intrathecal (IT) cholecystokinin (CCK), substance P (SP) and morphine (MO) on the nociceptive flexion reflex in the rat
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C-AFFERENT FIBRE EVOKED ACTIVITY AN INTRACELLULAR ANALYSIS. f,.J. Woolf and A. King* Department
IN THE DEEP DORSAL HORN: )I of
Anatomy,
University
College London, London WClE 6BT, U.K. Aim of Investigation: In addition to producing an excitation of dorsal horn ceils that contributes information concerning the onset, location and durainputs also produce prolonged tion of peripheral noxious stimul i, C-afferent post stimulus alterations in the responsiveness of the neurones including recruitment of novel inputs and the expansion of their receptive fields, We have now examined, increased excitability (Cook et al., Nature 1987). the effects of C-inputs on deep using intracellular recording techniques, dorsal horn neurones. Intracellular recordings with glass microelectrodes (60-100 Mfi) Methods: were made from neurones in laminae III to VI of the lumbar spinal cord in paralyzed decerebrate-spinal rats. Results: Activation of C-afferent fibres produces epsp’s leading to action -als in the majority of deep dorsal horn neurones. Repeated C-fibre stimulation (1 Hz) results in a labile response with ‘windup’ and ‘windown’ occurring. In a proportion of neurones the C-input is associated with a substantial depolarization that is, in some prolonged (tens of seconds), A-fibre input to these neurones cases sufficient to inactivate the neuron. is much more stable and is not associated with any sustained shift in membrane potential. Conclusions: C-afferent fibres have the capacity both to produce fast epsp’s and to modifv the excltabilitv of dorsal horn neurones by producinq slow Such C-afferent-induced excitability increases may contridepolarizations. bute to the central ‘sensitization’ that occurs during post injury hyperalgesia
(Woolf,
Nature,
EFFECTS
OF INTRATHECAL
1983).
(IT)
CHOLECYSTOKININ
(CCK),
SUBSTANCE
P (SP) AND MORPHINE (MO) ON THE NOCICEPTIVE FLEXION REFLEX IN THE RAT. Z. Wlesenfeld-Halllnl and R. Durantl*, IKarollnska inst., Sweden and
Dept. 2Dept
of of
Clan.
Clan.
Neurophyslol., Med. III, Univ.
141 86 Huddlnge, Florence, 501 34
455
Slide
11
Florence,
Italy
Aim of Investlgatlon: CCK 1s found In dorsal horn lnterneurons and in axons descending from the Edlnger-Westphal nucleus to the splnal cord, where it with SP (HBkfelt et al. In Neuronal Cholecystoklnin, 1985). CCKs coexists role in spinal function is unclear as It has been described to have analgesic (Jurna and Zetler, Europ. J. Pharmacol, 73:1981) as well as opiate antagonlstlc (Farls et al., Science, 219:1983) effects. The modulatory role of CCK on spinal nociceptlve reflex excitablllty was examined. Methods: The flexlon reflex to Intense electrlcal stimulation of the foot was recorded as EMG potentials from the hamstring muscles In decerebrate, splnallzed, unanaesthetlzed rats. Sulfated and desulfated CCK (sCCK and dCCK), SP, MO and naloxone (NAL) were injected IT and their effect on reflex excltabillty was quantified. Results: sCCK (long-lpg) had a brief (I-3min) facllltatory effect on the reflex, which was slmllar to SP (long). sCCK + SP had no synerglstlc Interaction at any dose level. MO (5ug) caused a brief (3min) facllltatlon, followed by a profound, long lasting (over Zhr) depression, which was readily reversed by NAL (25p,g), but not by sCCK. sCCK (lug) injected 2-3 mln prior to MO increased the facllltatory and decreased the depressive effect of MO slgnlflcantly. dCCK had a similar effect but at a higher dose. NAL administered prior to MO also decreased MOs lnhlbitory effect. Conclusions: sCCK prevents but does not reverse the depre&ve effect of MO on spinal excltablllty and may alter the balance of excitation-lnhlbltlon between various types~of dorsal horn cells involved In nociceptlve transmission.
C-AFFERENT FIBRE EVOKED ACTIVITY AN INTRACELLULAR ANALYSIS. f,.J. Woolf and A. King* Department
IN THE DEEP DORSAL HORN: )I of
Anatomy,
University
College London, London WClE 6BT, U.K. Aim of Investigation: In addition to producing an excitation of dorsal horn ceils that contributes information concerning the onset, location and durainputs also produce prolonged tion of peripheral noxious stimul i, C-afferent post stimulus alterations in the responsiveness of the neurones including recruitment of novel inputs and the expansion of their receptive fields, We have now examined, increased excitability (Cook et al., Nature 1987). the effects of C-inputs on deep using intracellular recording techniques, dorsal horn neurones. Intracellular recordings with glass microelectrodes (60-100 Mfi) Methods: were made from neurones in laminae III to VI of the lumbar spinal cord in paralyzed decerebrate-spinal rats. Results: Activation of C-afferent fibres produces epsp’s leading to action -als in the majority of deep dorsal horn neurones. Repeated C-fibre stimulation (1 Hz) results in a labile response with ‘windup’ and ‘windown’ occurring. In a proportion of neurones the C-input is associated with a substantial depolarization that is, in some prolonged (tens of seconds), A-fibre input to these neurones cases sufficient to inactivate the neuron. is much more stable and is not associated with any sustained shift in membrane potential. Conclusions: C-afferent fibres have the capacity both to produce fast epsp’s and to modifv the excltabilitv of dorsal horn neurones by producinq slow Such C-afferent-induced excitability increases may contridepolarizations. bute to the central ‘sensitization’ that occurs during post injury hyperalgesia
(Woolf,
Nature,
EFFECTS
OF INTRATHECAL
1983).
(IT)
CHOLECYSTOKININ
(CCK),
SUBSTANCE
P (SP) AND MORPHINE (MO) ON THE NOCICEPTIVE FLEXION REFLEX IN THE RAT. Z. Wlesenfeld-Halllnl and R. Durantl*, IKarollnska inst., Sweden and
Dept. 2Dept
of of
Clan.
Clan.
Neurophyslol., Med. III, Univ.
141 86 Huddlnge, Florence, 501 34
455
Slide
11
Florence,
Italy
Aim of Investlgatlon: CCK 1s found In dorsal horn lnterneurons and in axons descending from the Edlnger-Westphal nucleus to the splnal cord, where it with SP (HBkfelt et al. In Neuronal Cholecystoklnin, 1985). CCKs coexists role in spinal function is unclear as It has been described to have analgesic (Jurna and Zetler, Europ. J. Pharmacol, 73:1981) as well as opiate antagonlstlc (Farls et al., Science, 219:1983) effects. The modulatory role of CCK on spinal nociceptlve reflex excitablllty was examined. Methods: The flexlon reflex to Intense electrlcal stimulation of the foot was recorded as EMG potentials from the hamstring muscles In decerebrate, splnallzed, unanaesthetlzed rats. Sulfated and desulfated CCK (sCCK and dCCK), SP, MO and naloxone (NAL) were injected IT and their effect on reflex excltabillty was quantified. Results: sCCK (long-lpg) had a brief (I-3min) facllltatory effect on the reflex, which was slmllar to SP (long). sCCK + SP had no synerglstlc Interaction at any dose level. MO (5ug) caused a brief (3min) facllltatlon, followed by a profound, long lasting (over Zhr) depression, which was readily reversed by NAL (25p,g), but not by sCCK. sCCK (lug) injected 2-3 mln prior to MO increased the facllltatory and decreased the depressive effect of MO slgnlflcantly. dCCK had a similar effect but at a higher dose. NAL administered prior to MO also decreased MOs lnhlbitory effect. Conclusions: sCCK prevents but does not reverse the depre&ve effect of MO on spinal excltablllty and may alter the balance of excitation-lnhlbltlon between various types~of dorsal horn cells involved In nociceptlve transmission.