D-Arg1, D-Trp7,9, Leu11-substance P (spantide) does not antagonize substance P-induced hyperexcitability of the nociceptive flexion withdrawal reflex in the rat.

The effect of D-Arg1, D-Trp7,9, Leu11-substance P (SP) (spantide), a putative SP antagonist, on SP-induced facilitation of the flexion reflex was examined. The drugs were injected intrathecally (i.t.) in decerebrate, spinalized, unanaesthetized rats. Substance P (10 ng) caused an increase in reflex magnitude for about 5 min. Spantide (10 ng and 100 ng) also caused a facilitation of the reflex that was similar to SP. Spantide (10 ng) plus SP (10 ng) also had a similar excitatory effect. One microgram of spantide totally blocked the flexion reflex, which could not be reversed by SP, L-glutamate, L-aspartate or naloxone. It is concluded that spantide does not have an antagonistic effect on SP-induced changes in spinal reflex excitability. Some of the effects of i.t. spantide observed in behavioural studies may be due to a non-specific spinal motor block. It is suggested that the flexion reflex in the decerebrate, spinalized rat is a useful physiological model in studies of the effects of algesic and analgesic drugs at spinal level.

[1]  Z. Wiesenfeld‐Hallin.  Somatostatin and calcitonin gene-related peptide synergistically modulate spinal sensory and reflex mechanisms in the rat: Behavioral and electrophysiological studies , 1986, Neuroscience Letters.

[2]  Z. Wiesenfeld‐Hallin,et al.  Substance P and somatostatin modulate spinal cord excitability via physiologically different sensory pathways , 1986, Brain Research.

[3]  S. Sakurada,et al.  Intrathecal substance P analogue causes motor dysfunction in the rat , 1985, Neuropharmacology.

[4]  C. Post,et al.  Behavioural and antinociceptive effects of intrathecally injected substance P analogues in mice. , 1985, European journal of pharmacology.

[5]  C. Post,et al.  Antinociceptive and neurotoxic actions of substance P analogues in the rat's spinal cord after intrathecal administration , 1985, Neuroscience Letters.

[6]  E. Escher,et al.  Characterization of spinal actions of four substance P analogues. , 1985, European journal of pharmacology.

[7]  Patrick D. Wall,et al.  Muscle but not cutaneous C‐afferent input produces prolonged increases in the excitability of the flexion reflex in the rat. , 1984 .

[8]  J. Henry,et al.  Substance p anatogue blocks sp-induced facilitation of a spinal nociceptive reflex , 1984, Brain Research Bulletin.

[9]  R. Håkanson,et al.  Biological evaluation of substance P antagonists , 1984, British journal of pharmacology.

[10]  S. Hunt,et al.  Afferent C-fibres: physiological and biochemical correlations , 1984, Trends in Neurosciences.

[11]  T. Salt,et al.  The behavioural effects of intrathecally administered [d-PRO2,d-TRP7,9]-substance P, an analogue with presumed antagonist actions, in the rat , 1983, Neuropharmacology.

[12]  K. Folkers,et al.  Intrathecal (D-Pro2, D-Trp7,9)-SP elicits hypoalgesia and motor blockade in the rat and antagonizes noxious responses induced by substance P. , 1982, Acta physiologica Scandinavica.

[13]  M. Piercey,et al.  Sensory and motor functions of spinal cord substance P. , 1981, Science.

[14]  T. Hökfelt,et al.  Immunohistochemical evidence for a "neurotoxic" action of (D-Pro2, D-Trp7,9)-substance P, an analogue with substance P antagonistic activity. , 1981, Acta physiologica Scandinavica.

[15]  M. Otsuka,et al.  Identification by high-performance liquid chromatography of immunoreactive substance P released from isolated rat spinal cord , 1980, Neuroscience Letters.

[16]  T. Jessell,et al.  Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo , 1980, Nature.

[17]  Elizabeth Theriault,et al.  Capsaicin-evoked release of substance P from primary sensory neurons , 1979, Brain Research.

[18]  R. Dubner,et al.  Neurons that subserve the sensory-discriminative aspects of pain , 1977, Pain.

[19]  M. Randić,et al.  Effect of substance P in cat dorsal horn neurones activated by noxious stimuli , 1977, Brain Research.

[20]  S. Konishi,et al.  Release of substance P-like immunoreactivity from isolated spinal cord of newborn rat , 1976, Nature.

[21]  J. Henry,et al.  Effects of substance P on functionally identified units in cat spinal cord , 1976, Brain Research.

[22]  S. Konishi,et al.  Substance P and excitatory transmitter of primary sensory neurons. , 1976, Cold Spring Harbor symposia on quantitative biology.

[23]  T. Hökfelt,et al.  Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons , 1975, Brain Research.

[24]  K. Krnjević,et al.  Substance P and spinal neurones. , 1975, Canadian journal of physiology and pharmacology.

[25]  Tomoyuki Takahashi,et al.  Regional distribution of substance P in the spinal cord and nerve roots of the cat and the effect of dorsal root section , 1975, Brain Research.

[26]  F. Lembeck,et al.  Substance P: A Polypeptide of Possible Physiological Significance, Especially Within the Nervous System , 1962 .