neuropeptide and pain

John H. johnhkm at
Sat Mar 18 01:59:54 EST 2000

Fair enough Olivier! Below, some extracts from first two pageson pubmed
under search string "substance P And pain" 1108 hits. Didn't look too
closely but I suggest you check their refs and also find the journal home
pages and do searches there(my next search step). Once you want specifics,
medline does become cumbersome ... .

Hope this helps,

John H.
Remove 4x

Eur J Pain 1999 Jun;3(2):93-102 Related Articles, Books

Experimental human muscle pain induced by intramuscular injections of
bradykinin, serotonin, and substance P.

Babenko V, Graven-Nielsen T, Svensson P, Drewes AM, Jensen TS,
Arendt-Nielsen L

Centre for Sensory-Motor Interaction, Laboratory for Experimental Pain
Research, Aalborg University, Aalborg, Denmark

[Record supplied by publisher]

After intramuscular (m. tibialis anterior) injection of three different
algogenic substances, the pain intensity was continuously scored on a visual
analogue scale (VAS) in eight volunteers. The subject drew the distribution
of the local and referred pain areas on a map. Four times within the first
hour after injection, the pressure pain-thresholds (PPTs) and supra
pressure-pain thresholds were assessed at the injection point, 2 cm distal
from the injection site, at the arm, and at the contralateral leg.
Measurements were done before and after injection of 0.5 ml of the algogenic
substance [bradykinin (BKN), serotonin (5-HT), substance P (SP)], and
isotonic saline as control. Cutaneous sensitivity to mechanical stimuli was
assessed with a Von Frey hair at the same location as PPT determinations.The
pain intensity (VAS-peak) after BKN (2, 4, and 10 nmol) and 5-HT (2, 4, and
20 nmol) was significantly higher (p< 0.05) than after SP (0.2, 0.4, and 0.8
nmol) and isotonic saline. The VAS-peak after infusions of hypertonic saline
was significantly higher (p< 0.05) compared with VAS-peaks after all other
substances. A significantly larger (p< 0.05) local pain area was found after
BKN compared with isotonic saline. After injections of hypertonic saline,
the offsets of evoked pain were significantly longer (p< 0.05) and the local
and referred pain areas were significantly larger (p< 0.05) compared with
all other substances. There was no dose-response relation between the pain
intensity and the different doses of BKN, 5-HT, and SP. PPTs and skin
sensitivity were not affected by any of the injections.We conclude that
under the present experimental conditions, BKN and 5-HT can produce low
levels of muscle pain after intramuscular injection. In the used
concentrations, however, BKN, 5-HT, and SP did not generate cutaneous or
muscular hyperalgesia. Copyright 1999 European Federation of Chapters of the
International Association for the Study of Pain.

PMID: 10700339


2 : Brain 2000 Mar;123 Pt 3:601-19 Related Articles, Books, LinkOut

Cytoarchitectonic and immunohistochemical characterization of a specific
pain and temperature relay, the posterior portion of the ventral medial
nucleus, in the human thalamus.

Blomqvist A, Zhang ET, Craig AD

Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of
Health Sciences, University of Linkoping, Sweden. andbl at

Previous studies in the macaque monkey have identified a thalamic nucleus,
the posterior portion of the ventral medial nucleus (VMpo), as a dedicated
lamina I spinothalamocortical relay for pain and temperature sensation. The
dense plexus of calbindin-immunoreactive fibres that characterizes VMpo in
primates enables its homologue to be identified in the human thalamus by
immunohistochemical labelling for calbindin. We have now analysed in detail
the cytoarchitectonic characteristics of VMpo and its relationship with
immunoreactivity for calbindin, substance P and calcitonin gene-related
peptide (CGRP) in the human thalamus. The area in the posterolateral
thalamus in which dense calbindin-immunoreactive fibre terminations are
present coincides nearly completely with a distinct region that contains
small to medium-sized cells with round or oval shapes that are aggregated in
clusters separated by cell sparse areas. This region, which we identify as
VMpo, is located posteromedial to the ventral posterior lateral (VPL) and
ventral posterior medial (VPM) nuclei, ventral to the anterior pulvinar and
centre median nuclei, lateral to the limitans and parafascicular nuclei and
dorsal to the medial geniculate nucleus. Calbindin-immunoreactive fibres
enter VMpo from the spinal lemniscus and form large patches of dense
terminal-like staining over clusters of VMpo neurons. A few of these
clusters also display terminal-like substance P labelling. Small bursts of
CGRP staining are intercalated between the calbindin-labelled clusters, but
there is little or no overlap between these two markers. CGRP
immunoreactivity is also present over small, non-clustered neurons in the
calbindin-negative area that separates VMpo from the VPL and VPM nuclei,
which we denote as the posterior nucleus (Po). These observations provide a
concise description of VMpo in the human thalamus. Further, they suggest
that the lamina I spinothalamic tract fibres (represented by calbindin and
probably also substance P immunoreactivity) and vagal-solitary-parabrachial
afferents (represented by CGRP immunoreactivity) form closely related, but
separate, termination fields that can be considered to represent different
aspects of enteroceptive information regarding the physiological status of
the tissues and organs of the body. The location of VMpo and the adjacent Po
fits with clinical descriptions of the thalamic area from which pain,
temperature and visceral sensations can be evoked by microstimulation, and
where nociceptive and thermoreceptive neurons have been recorded in humans.
It also corresponds to the area in which infarcts cause analgesia and
thermoanaesthesia and can lead to the paradoxical development of central

PMID: 10686182, UI: 20153287


3 : JAMA 2000 Jan 12;283(2):187-8 Related Articles, Books

Loss of nerve: a molecular approach to better treatment of chronic pain.

Friedrich MJ

Publication Types:

PMID: 10634324, UI: 20097790


4 : Pain 2000 Jan;84(1):13-20 Related Articles, Books, LinkOut

Moxonidine, a selective imidazoline/alpha(2) adrenergic receptor agonist,
synergizes with morphine and deltorphin II to inhibit substance P-induced
behavior in mice.

Fairbanks CA, Posthumus IJ, Kitto KF, Stone LS, Wilcox GL

Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455,

The alpha(2) adrenergic receptor (AR) class of catecholamine/imidazoline (I)
agonists, such as norepinephrine and clonidine, produce spinal
antinociceptive synergy when co-administered with opioids. We have observed
that intrathecally administered moxonidine, a selective I(1)/alpha(2) (AR)
agonist, produces antinociception. The present experiments tested moxonidine
for ability to synergize with morphine, deltorphin II, and DAMGO
(Tyr-D-Ala-NMe-Phe-Gly(ol)) to inhibit substance P-elicited nociceptive
behavior in Institute of Cancer Research mice. Moxonidine, morphine,
deltorphin II, and DAMGO inhibited substance P-elicited nociceptive behavior
with full efficacy. Effective dose 50% (ED(50)) values were calculated and
equi-effective dose ratios of the combinations moxonidine-morphine,
moxonidine-deltorphin II, and moxonidine-DAMGO were determined. The
interactions were tested by isobolographic analysis. The observed ED(50)
values of the combinations were statistically compared against their
respective calculated theoretical additive ED(50) values. The combinations
of moxonidine-morphine and moxonidine-deltorphin II resulted in significant
leftward shifts in the dose-response curves compared to those of each
agonist administered separately. The ED(50) values of the dose-response
curves of these combinations were significantly less than the corresponding
calculated theoretical additive ED(50) values; these results indicated that
moxonidine synergizes with both morphine and deltorphin II. In contrast,
combining moxonidine with DAMGO did not increase the potencies of the
agonists (in combination) when compared to the potencies of each agonist
administered separately. These results indicated that the moxonidine-DAMGO
interaction is subadditive. Collectively, these data demonstrate that
moxonidine combined with some opioid agonists produces spinal
antinociceptive synergy. Spinally administered moxonidine-opioid
combinations may prove an effective therapeutic strategy to manage pain.

PMID: 10601668, UI: 20070137


5 : Life Sci 1999;65(22):2269-87 Related Articles, Books

The role of dopamine in the nucleus accumbens in analgesia.

Altier N, Stewart J

Center for Studies in Behavioral Neurobiology, Department of Psychology,
Concordia University, Montreal, Quebec, Canada.

Opioid and psychostimulant drugs have long been used for the relief of
chronic pain in the clinical situation. Animal studies confirm that these
drugs alleviate persistent or tonic pain. Little is known, however, about
the neural systems underlying the suppression of tonic pain except that they
are different from those mediating the suppression of phasic (i.e., sharp
and short-lasting) pain. Although spinal and brainstem-descending pain
suppression mechanisms play a role in mediating the inhibition of tonic
pain, it appears that this response is additionally mediated by the
activation of mechanisms lying rostral to the brainstem. Recent studies
suggest that the activation of mesolimbic dopamine (DA) neurons, arising
from the cell bodies of the ventral tegmental area (VTA) and projecting to
the nucleus accumbens (NAcc), plays an important role in mediating the
suppression of tonic pain. Other studies suggest that this pain-suppression
system involving the activation of mesolimbic DA neurons is naturally
triggered by exposure to stress, through the endogenous release of opioids
and substance P (SP) in the midbrain.

Publication Types:
Review, tutorial

PMID: 10597883, UI: 20064753


6 : J Neurosci 1999 Dec 15;19(24):10886-97 Related Articles, Books, LinkOut

Neurochemical and cellular reorganization of the spinal cord in a murine
model of bone cancer pain.

Schwei MJ, Honore P, Rogers SD, Salak-Johnson JL, Finke MP, Ramnaraine ML,
Clohisy DR, Mantyh PW

Neurosystems Center, Department of Preventive Sciences, Minneapolis,
Minnesota 55455, USA.

The cancer-related event that is most disruptive to the cancer patient's
quality of life is pain. To begin to define the mechanisms that give rise to
cancer pain, we examined the neurochemical changes that occur in the spinal
cord and associated dorsal root ganglia in a murine model of bone cancer.
Twenty-one days after intramedullary injection of osteolytic sarcoma cells
into the femur, there was extensive bone destruction and invasion of the
tumor into the periosteum, similar to that found in patients with osteolytic
bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there
was a massive astrocyte hypertrophy without neuronal loss, an expression of
dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal
horn. Additionally, normally non-noxious palpation of the bone with cancer
induced behaviors indicative of pain, the internalization of the substance P
receptor, and c-Fos expression in lamina I neurons. The alterations in the
neurochemistry of the spinal cord and the sensitization of primary afferents
were positively correlated with the extent of bone destruction and the
growth of the tumor. This "neurochemical signature" of bone cancer pain
appears unique when compared to changes that occur in persistent
inflammatory or neuropathic pain states. Understanding the mechanisms by
which the cancer cells induce this neurochemical reorganization may provide
insight into peripheral factors that drive spinal cord plasticity and in the
development of more effective treatments for cancer pain.

PMID: 10594070, UI: 20063043


7 : Scand Cardiovasc J 1999;33(5):295-9 Related Articles, Books

Acute ischemic chest pain is not associated with increased calcitonin
gene-related peptide (CGRP) levels in peripheral plasma nor in the coronary

Wahrborg P, Eliasson T, Edvardsson N, Ekman R, Mannheimer C, Hedner T

Division of Cardiology, Sahlgrenska University Hospital, Goteborg, Sweden.

Calcitonin gene-related peptide (CGRP) and substance P co-exist in
capsaicin-sensitive primary sensory neurons and are released from the
myocardium after activation of sensory nerve fibres as well as by ischemia
in animals. This study was undertaken to try to clarify the potential
involvement of immunoreactive (ir) CGRP in anginal pain and myocardial
ischemia in humans. One clinical group (n = 87) and one experimental group
(n = 14) were studied. The clinical group was admitted to a coronary care
unit with suspected or definite acute myocardial infarction (AMI). The
experimental group consisted of patients with severe angina pectoris (NYHA
III-IV). This group was subjected to atrial pacing up to the appearance of
angina pectoris. Mean irCGRP levels at admission for the clinical group with
and without AMI showed no significant difference. Neither were any
significant differences found in irCGRP concentrations between patients with
pain as compared to those without pain or in the group who had had chest
pain >30 min before hospital admission as compared to those with chest pain
<30 min. Extraction ratios for lactate and irCGRP was calculated in the
experimental group. No statistically significant covariance was found
between irCGRP extraction ratio and lactate extraction ratio (r(xy)
= -0.006) at the time of appearance of angina during atrial pacing. Despite
the facts that CGRP may be liberated by a variety of physiological stimuli
and may act as a potent vasodilator in the human vasculature, no evidence
has been found in this study that CGRP release is increased as a consequence
of ischemia or ischemic pain.

PMID: 10540919, UI: 20006932


8 : Pain 1999 Dec;83(3):541-7 Related Articles, Books, LinkOut

Plasma levels of substance P, neuropeptide Y and vasoactive intestinal
polypeptide in patients with chronic tension-type headache.

Ashina M, Bendtsen L, Jensen R, Ekman R, Olesen J

Department of Neurology, Glostrup Hospital, University of Copenhagen,
DK-2600 Glostrup, Copenhagen, Denmark. ashina at

Animal and human studies have shown that substance P (SP), neuropeptide Y
(NPY) and vasoactive intestinal polypeptide (VIP) are involved in the
pathophysiology of acute and chronic pain conditions. The primary aim of the
present study was to compare plasma levels of SP, NPY and VIP in external
jugular vein between patients with chronic tension-type headache and healthy
controls. The secondary aim was to examine plasma levels of these
neuropeptides in relation to headache state. In addition, we wanted to study
the relation between cranial circulation (jugular vein) and peripheral
circulation (antecubital vein). Blood from the external jugular and
antecubital vein was drawn from 20 patients with chronic tension-type
headache and 20 healthy controls. Plasma SP in patients, 2.0 (1.4-2.2)
pmol/l, did not differ significantly from plasma SP in controls, 1.7
(1.1-2.1) pmol/l, (P=0.44). No significant differences were found between SP
levels on days with headache, 1.5 (0.3-1.7) pmol/l, and SP levels on days
without headache, 1.7 (1.1-1. 9) pmol/l, (P=0.06). Plasma NPY in patients,
118+/-3 pmol/l, did not differ significantly from plasma NPY in controls,
113+/-5 pmol/l, (P=0.40). There was no difference between NPY levels on days
with headache, 120+/-3 pmol/l, and on days without headache, 118+/-3 pmol/l,
(P=0.73). VIP levels in patients, 6 (4-7) pmol/l, did not differ
significantly from VIP levels in controls, 5 (5-7) pmol/l, (P=0.50). No
significant differences were found between VIP levels measured on days with
headache, 5 (4-6) pmol/l, and VIP levels measured on days without headache,
6 (4-7) pmol/l, (P=0.81). Plasma levels of SP, NPY and VIP did not
significantly differ between the peripheral and the cranial circulation
neither in patients nor in controls (0.05). In summary, the present study
indicates that plasma levels of SP, NPY and VIP are normal in chronic
tension-type headache patients and largely unrelated to headache state.

PMID: 10568863, UI: 20038205


Olivier Joubert <ojoub at> wrote in message
news:8atfak$ljc$1 at
> --
> Olivier Joubert
> 4, avenue St Exupéry
> 21800 Chevigny St Sauveur
> France
> John H. <johnhkm at> a écrit dans le message :
> 8at8kr$f5e$2 at
> >
> > <dag.stenberg at> wrote in message
> > news:8arbgp$nuq$1 at
> > > Olivier Joubert <ojoub at> wrote:
> > > > :I am in Master of biochemistry and I have a statement on the
> > neuropeptides
> > > > :involved in pain to do. May you help me??
> > > > :Where can I search or have you some advice?
> > > > :
> > >
> > > This is the usual place to start:
> > >
> > >
> > > I hope it works for you
> >
> > Works for me. Do a general search also, there are a number of sites on
> pain.
> >
> > John H.
> Yes I know that medline is a right place to search, but if I type
> neuropeptide and pain I get about 200000 references!!
> It's not easy to make a choice when you have a number of references!!
> regards
> olivier
> >

More information about the Neur-sci mailing list