Distinguishable effects of intrathecal dynorphins, somatostatin, neurotensin and s-calcitonin on nociception and motor function in the rat

Spampinato, Santi; Romualdi, Patrizia; Candeletti, Sanzio; Cavicchini, E.; Ferri, Sergio Solbes

doi:10.1016/0304-3959(88)90281-3

Cited by 53 publications

(30 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies had shown that intrathecal injection of NT induces antinociception in a variety of analgesic tests including hotplate, tail-flick, and writhing tests (Clineschmidt et al, 1982;Martin and Naruse, 1982;Yaksh et al, 1982;Hylden and Wilcox, 1983;Spampinato et al, 1988). Some of these effects are likely mediated via NTS1, because mice deficient in NTS1 expression exhibited reduced antinociception in the hotplate test (Tyler et al, 1998;Pettibone et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…At the spinal level, intrathecal administration of NT results in an increase in nociceptive threshold in the hotplate test and alters the tail-flick and acetic acid-induced writhing response latency (Martin et al, 1981;Clineschmidt et al, 1982;Martin and Naruse, 1982;Yaksh et al, 1982;Hylden and Wilcox, 1983;Spampinato et al, 1988). In support of a physiological counterpart to these effects of exogenous NT, high concentrations of NTimmunoreactive cell bodies and axon terminals have been detected in the superficial layers of the dorsal horn of the spinal cord (Uhl et al, 1979;Gibson et al, 1981;Hunt et al, 1981;Ninkovic et al, 1981;Seybold and Elde, 1982;Yaksh et al, 1982;Reinecke et al, 1983;Difiglia et al, 1984;Urban and Smith, 1993).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Potent Spinal Analgesia Elicited through Stimulation of NTS2 Neurotensin Receptors

Sarret¹,

Esdaile²,

Perron³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

Intrathecal administration of the neuropeptide neurotensin (NT) was shown previously to exert antinociceptive effects in a variety of acute spinal pain paradigms including hotplate, tail-flick, and writhing tests. In the present study, we sought to determine whether some of these antinociceptive effects might be elicited via stimulation of low-affinity NTS2 receptors. We first established, using immunoblotting and immunohistochemical techniques, that NTS2 receptors were extensively associated with putative spinal nociceptive pathways, both at the level of the dorsal root ganglia and of the superficial layers of the dorsal horn of the spinal cord. We then examined the effects of intrathecal administration of NT or selective NTS2 agonists on acute thermal pain. Both NT and NTS2 agonists, levocabastine and Boc-Arg-Arg-Pro-Tyr⌿(CH 2 NH)Ile-Leu-OH (JMV-431), induced dose-dependent antinociceptive responses in the tail-flick test. The effects of levocabastine and of JMV-431 were unaffected by coadministration of the NTS1-specific antagonist 2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxy-phenyl)pyrazol-3-yl)carboxylamino]tricyclo)3.3.1.1. 3.7)-decan-2-carboxylic acid (SR48692), confirming that they were NTS2 mediated. In contrast, the antinociceptive effects of NT were partly abolished by coadministration of SR48692, indicating that NTS1 and NTS2 receptors were both involved. These results suggest that NTS2 receptors play a role in the regulation of spinal nociceptive inputs and that selective NTS2 agonists may offer new avenues for the treatment of acute pain.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Potent Spinal Analgesia Elicited through Stimulation of NTS2 Neurotensin Receptors

Sarret¹,

Esdaile²,

Perron³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…NT has been shown to have antinociceptive effects (52)(53)(54). These effects have been related to NT-containing dorsal horn neurons (55)(56)(57) and NT binding sites on dorsal horn neurons (58,59).…”

Section: Discussionmentioning

confidence: 99%

Electrophysiological studies on rat dorsal root ganglion neurons after peripheral axotomy: Changes in responses to neuropeptides

Grillner

Hökfelt

1997

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The effect of three peptides, galanin, sulfated cholecystokinin octapeptide, and neurotensin (NT), was studied on acutely extirpated rat dorsal root ganglia (DRGs) in vitro with intracellular recording techniques. Both normal and peripherally axotomized DRGs were analyzed, and recordings were made from C-type (small) and A-type (large) neurons. Galanin and sulfated cholecystokinin octapeptide, with one exception, had no effect on normal C-and A-type neurons but caused an inward current in both types of neurons after sciatic nerve cut. In normal rats, NT caused an outward current in C-type neurons and an inward current in A-type neurons. After sciatic nerve cut, NT only caused an inward current in both C-and A-type neurons. These results suggest that (i) normal DRG neurons express receptors on their soma for some but not all peptides studied, (ii) C-and A-type neurons can have different types of receptors, and (iii) peripheral nerve injury can change the receptor phenotype of both C-and A-type neurons and may have differential effects on these neuron types.Peripherally axotomized animals represent one model to study neuropathic pain (1). A damaged nerve can contribute actively to chronic pain by generating abnormal discharges and by amplifying and distorting naturally generated signals (2, 3), whereby the soma of dorsal root ganglion (DRG) neurons can become a site of abnormal impulse generation (4, 5).Peripherally, nerve injury also causes changes in peptide expression in DRG neurons. Thus, the synthesis of substance P (6) and calcitonin gene-related peptide (7, 8) is reduced, and that of vasoactive intestinal polypeptide (9), galanin (GAL) (10), and neuropeptide tyrosine (NPY) (11) is increased. Also, the expression of neuropeptide receptors such as cholecystokinin B-type (CCK B ) receptors (12) and NPY type 1 receptors (Y1-Rs) (13) is changed. To what extent, if at all, these changes in chemical phenotype are related to pain is not well understood, but a better insight into the chemical machinery in primary sensory neurons after peripheral axotomy may provide a better understanding of pain syndromes accompanying peripheral nerve injury and could lead to improved treatment strategies.Using electrophysiological techniques, the effects of peptides such as enkephalin (14) and GAL (15) have been studied on cultured DRG neurons. In the present study we administered three different peptides, GAL (16), sulfated CCK octapeptide (CCK-8S) (17), and neurotensin (NT) (18) onto rat DRG somata in vitro and monitored responses using intracellular recording techniques. Acutely extirpated DRGs from both normal rats and ganglia removed 5-7 days after peripheral axotomy were studied. We previously have reported results on the effect of NPY and NT on normal ganglia using the same intracellular recording technique (19). MATERIALS AND METHODSAnimals and in Vitro Preparation. In Sprague-Dawley rats (female, 100-200 g body weight; n ϭ 76), the sciatic nerve was transected bilaterally at mid-thigh level under deep anesthesia [s...

show abstract

“…If neurotensin is applied directly to the cord dorsum it causes expression of the proto-oncogene product c-fos in a few neurons, and this is consistent with an excitatory action on these cells (Leah et al, 1989). When applied by intrathecal injection, neurotensin has an apparent analgesic action, although this depends on the test that is used (Yaksh et al, 1982;Spampinato et al, 1988).…”

Section: Methodological Considerationsmentioning

confidence: 99%

Immunocytochemical evidence that neurotensin is present in glutamatergic neurons in the superficial dorsal horn of the rat

et al. 1994

View full text Add to dashboard Cite

In order to determine whether glutamate is enriched in neurotensin- containing axons in the superficial dorsal horn of the rat spinal cord, we have carried out preembedding immunocytochemistry with an antiserum to neurotensin and then used a postembedding immunogold method with antiserum to glutamate. The immunogold label (corresponding to glutamate-like immunoreactivity) over 40 neurotensin-immunoreactive boutons in laminae I and II of the lumbar dorsal horn was compared with that over nearby axons that formed asymmetrical or symmetrical synapses. In addition, for 20 of these boutons, the labeling was compared with that over mossy and parallel fiber terminals (both of which are thought to use glutamate as a transmitter) from sections of cerebellum that had been processed together with those of spinal cord. Glutamate-like immunoreactivity was consistently high over neurotensin- immunoreactive boutons relative to most surrounding profiles. Immunostaining over these boutons was slightly (11%) lower than that over matched terminals that formed asymmetrical synapses, but considerably higher than that over the terminals that formed symmetrical synapses. The level of glutamate immunoreactivity in neurotensin-immunoreactive boutons in dorsal horn was similar to that in cerebellar parallel fiber terminals, but significantly lower than that in mossy fiber terminals. These results suggest that glutamate is a transmitter used by neurotensin-immunoreactive axons in the dorsal horn, and since these axons are thought to be largely or entirely derived from neurotensin-containing neurons in laminae I-III, they provide immunocytochemical evidence for a population of excitatory glutamatergic neurons in this region.

show abstract

Distinguishable effects of intrathecal dynorphins, somatostatin, neurotensin and s-calcitonin on nociception and motor function in the rat

Cited by 53 publications

References 41 publications

Potent Spinal Analgesia Elicited through Stimulation of NTS2 Neurotensin Receptors

Potent Spinal Analgesia Elicited through Stimulation of NTS2 Neurotensin Receptors

Electrophysiological studies on rat dorsal root ganglion neurons after peripheral axotomy: Changes in responses to neuropeptides

Immunocytochemical evidence that neurotensin is present in glutamatergic neurons in the superficial dorsal horn of the rat

Contact Info

Product

Resources

About