APITOXINA ANALGESICO
| 1: J Nat Prod. 2005 Jul;68(7):1031-6. |
Myo-inositol-derived
glycolipids with anti-inflammatory activity from Solanum lanceolatum.
Herrera-Salgado Y,
Garduno-Ramirez ML,
Vazquez L, Rios MY, Alvarez L.
Centro de Investigaciones Quimicas, Universidad Autonoma del Estado de Morelos,
Avenida Universidad 1001, Chamilpa, 62210, Cuernavaca, Morelos, Mexico.
Lanceolitols A1-A7 (1-7) and
B1-B7 (9-15), two series of new myo-inositol-derived glycolipid analogues,
in which a sugar moiety is replaced by a fatty acid esterified myo-inositol
moiety, were isolated from the leaves of Solanum lanceolatum. Their structures
were elucidated on the basis of spectroscopic analysis (1H NMR,
| 2: Brain Res. 2005 May 10;1043(1-2):231-5. |
Evidence
for peripherally antinociceptive action of propofol in rats: behavioral and
spinal neuronal responses to subcutaneous bee venom.
Sun
YY, Li KC, Chen
J.
In the present study, behavioral and in vivo electrophysiological methods
were used to examine the peripheral effects of propofol on tonic ongoing pain-related
responses produced by subcutaneous bee venom-induced inflammatory pain state.
Local administration of 0.5 microg propofol produced significant suppression
of the well-established ongoing pain responses in both conscious rats and
dorsal horn nociceptive neurons. The locally antinociceptive action of propofol
is not caused by systemic effect, because contralateral administration of
the same dose of drug did not produce any effect. This result indicates that
besides central actions, propofol has peripherally antinociceptive action
as well.
| 3: Evid Based Complement Alternat Med. 2005 Mar;2(1):79-84. |
An Overview
of Bee Venom Acupuncture in the Treatment of Arthritis.
Lee
JD, Park
HJ, Chae
Y, Lim
S.
Bee venom acupuncture (BVA), as a kind of herbal acupuncture, exerts not only
pharmacological actions from the bioactive compounds isolated from bee venom
but also a mechanical function from acupuncture stimulation. BVA is growing
in popularity, especially in
| 4: Pharmacol Res. 2005 Feb;51(2):183-8. |
Antinociceptive
mechanisms associated with diluted bee venom acupuncture (apipuncture) in
the rat formalin test: involvement of descending adrenergic and serotonergic
pathways.
Kim
HW, Kwon
YB, Han
HJ, Yang
IS, Beitz
AJ, Lee
JH.
Department of Veterinary Physiology, College of Veterinary Medicine and School
of Agricultural Biotechnology, Seoul National University, San 56-1, Shilim-dong,
Kwanak-gu, Seoul 151-742, South Korea.
In a previous report, subcutaneous injection of diluted bee venom (dBV) into
a specific acupuncture point (Zusanli, ST36), a procedure termed apipuncture,
was shown to produce an antinociceptive effect in the rat formalin pain model.
However, the central antinociceptive mechanisms responsible for this effect
have not been established. Traditional acupuncture-induced antinociception
is considered to be mediated by activation of the descending pain inhibitory
system (DPIS) including initiation of its opioidergic, adrenergic and serotonergic
components. The purpose of the present study was to investigate whether the
antinociceptive effect of apipuncture is also mediated by the DPIS. Behavioral
experiments verified that apipuncture significantly reduces licking behavior
in the late phase of formalin test in rats. This antinociceptive effect of
apipuncture was not modified by intrathecal pretreatment with naltrexone (a
non-selective opioid receptor antagonist), prazosin (an alpha1 adrenoceptor
antagonist) or propranolol (an beta adrenoceptor antagonist). In contrast,
intrathecally injected idazoxan (an alpha2 adrenoceptor antagonist) or intrathecal
methysergide (a serotonin receptor antagonist) significantly reversed apipuncture-induced
antinociception. These results suggest that apipuncture-induced antinociception
is produced by activation of alpha2 adrenergic and serotonergic components
of the DPIS.
PMID: 15629266 [PubMed - indexed for MEDLINE]
| 5: J Vet Sci. 2004 Dec;5(4):309-18. |
General pharmacological
profiles of bee venom and its water soluble fractions in rodent models.
Kim HW, Kwon YB, Ham TW, Roh DH, Yoon SY, Kang SY, Yang IS, Han HJ, Lee HJ, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Seoul 151-742, Korea.
Recently, the antinociceptive and anti-inflammatory efficacy of bee venom
(BV, Apis mellifera) has been confirmed in rodent models of inflammation and
arthritis. Interestingly, the antinociceptive and anti-inflammatory effect
of whole BV can be reproduced by two water-soluble fractions of BV (>20
kDa:BVAF1 and<10 kDa: BVAF3). Based on these scientific findings, BV and
its effective water-soluble fractions have been proposed as potential anti-inflammatory
and antinociceptive pharmaceuticals. While BV's anti-inflammatory and antinociceptive
properties have been well documented, there have been no careful studies of
potential, side effects of BV and its fractions when administered in the therapeutic
range (BV, 5 microgram/kg; BVAF1, 0.2 microgram/kg: BVAF3, 3 microgram/kg;
subcutaneous or intradermal). Such information is critical for future clinical
use of BV in humans. Because of this paucity of information, the present study
was designed to determine the general pharmacological/physiological effects
of BV and its fractions administration on the rodent central nervous, cardiovascular,
respiratory and gastrointestinal system. Subcutaneous BV and its fractions
treatment did not produce any significant effects on general physiological
functions at the highest dose tested (200-fold and 100-fold doses higher than
that used clinically, respectively) except writhing test. These results demonstrate
that doses of BV or BV subfractions in the therapeutic range or higher can
be used as safe antinociceptive and anti-inflammatory agents.
PMID: 15613814 [PubMed - indexed for MEDLINE]
| 6: Mol Cells. 2004 Apr 30;17(2):329-33. |
Bee venom
acupoint stimulation increases Fos expression in catecholaminergic neurons
in the rat brain.
Kwon
YB, Han
HJ, Beitz
AJ, Lee
JH.
Department of Veterinary Physiology, College of Veterinary Medicine and School
of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea.
Fos immunocytochemistry was combined with tyrosine hydroxylase (TH) or dopamine-beta-hydroxylase
(DBH) immunolabeling to examine brainstem catecholaminergic neuronal activation
resulting from bee venom (BV) stimulation of the Zusanli acupoint (ST36) in
Sprague-Dawley rats. BV injection into the Zusanli acupoint caused increased
Fos expression in catecholaminergic neurons located in the hypothalamic arcuate
nucleus (Arc), the dorsal raphe (DR), the A5 cell group (A5) and the locus
coeruleus (LC). BV acupoint stimulation significantly increased Fos-TH double-labeled
neurons in the Arc, LC and DR. Fos-DBH positive neurons were also increased
by BV acupoint stimulation in the LC and A5. In contrast BV stimulation of
a non-acupoint only increased Fos expression and Fos-TH double-labeled neurons
in the Arc. These data indicate that BV acupoint stimulation activates brainstem
catecholaminergic neurons and that this activation underlies BV acupoint-induced
antinociception.
PMID: 15179050 [PubMed - indexed for MEDLINE]
| 7: Zhong Yao Cai. 2003 Jun;26(6):456-8. |
[Advances in the
study of bee venom and its clinical uses]
[Article in Chinese]
Liu
H, Tong
F.
College of Zoological Sciences,
Publication Types:
· Review
PMID: 14669739 [PubMed - indexed for MEDLINE]
| 8: Sheng Li Xue Bao. 2003 Oct 25;55(5):516-24. |
Effects of
intravenous Injections Paederiae and Stauntonia on spontaneous pain, hyperalgesia
and inflammation induced by cutaneous chemical tissue injury in the rat.
Peng
XL, Gao
XL, Chen
J, Huang
X, Chen
HS.
To study whether commercial traditional Chinese medicinal preparations Injection
Paederiae (IP) or Injection Stauntonia (IS) has anti-nociceptive and/or anti-inflammatory
effects, we used two persistent pain models (bee venom and formalin test)
to evaluate the systemic effects of IP or IS on the chemical tissue injury-induced
persistent spontaneous pain-related responses (PSPR), primary thermal/mechanical
hyperalgesia and inflammation in conscious rats. Injection of bee venom (BV,
0.1 mg, 50 microl) into the plantar surface of one hind paw resulted in not
only a 1-h monophasic PSPR such as flinching reflex in the injected paw and
a subsequent period of 3-4 days primary heat and mechanical hyperalgesia,
but also a marked sign of inflammation, including redness and swelling of
the plantar surface in the injected paw. Intraplantar injection of formalin
produced two phases of PSPR as reported previously. Systemic pre-treatment
with three doses of IP (0.32, 1.6 and 9.0 ml/kg, 500%) or IS (0.32, 1.6 and
9.0 ml/kg, 250%) produced a dose-dependent suppression of the BV- or formalin-induced
flinching reflex of 1 h time course as compared with the saline control group.
Post-treatment with IP or IS 5 min after BV injection also produced a significant
suppression of the flinching reflex in both BV test and formalin test respectively,
as compared with the control group. However, neither pre- nor post-treatment
with IP or IS produced any significantly suppressive effect on the BV-induced
primary heat and mechanical hyperalgesia and inflammation. The analgesia produced
by IP or IS was not mediated by the endogenous opioid receptors since naloxone,
a non-selective opioid receptor antagonist, had no reversal effect on the
IP and IS-produced analgesia in the BV-induced PSPR. Our present results suggest
that IP or IS might prevent and relieve clinical persistent spontaneous pain,
but without any anti-nociceptive and anti-inflammatory effects on the primary
heat hyperalgesia, mechanical hyperalgesia, as well as inflammatory responses.
The BV test might be a useful model of pain to evaluate and screen anti-nociceptive
and anti-inflammatory effects of certain compounds of the Chinese medicinal
herbs on the pathological origins of pain.
| 9: Neuroscience. 2003;121(2):459-72. |
Differential
antinociceptive effects induced by a selective cyclooxygenase-2 inhibitor
(SC-236) on dorsal horn neurons and spinal withdrawal reflexes in anesthetized
spinal rats.
You
HJ, Morch
CD, Chen
J, Arendt-Nielsen
L.
Center for Sensory-Motor Interaction, Laboratory for Experimental Pain Research,
Aalborg University, Fredrik Bajers Vej 7D-3, DK-9220, Aalborg, Denmark. lan@smi.auc.dk
The aim of present study was to examine the effect of a selective cyclooxygenase-2
(COX-2) inhibitor SC-236 (4 mg/kg) on the simultaneous responsiveness of spinal
wide-dynamic range (WDR) neurons and single motor units (SMUs) from gastrocnemius
soleus muscles to mechanical stimuli (pressure and pinch) and repeated suprathreshold
(1.5xT, the intensity threshold) electrical stimuli with different frequencies
(3 Hz, 20 Hz) under normal conditions and bee venom (BV, 0.2 mg/50 microl)-induced
inflammation and central sensitization. During normal conditions, the responses
of SMUs, but not WDR neurons, to mechanical and repeated electrical stimuli
(3 Hz, wind-up) were depressed by systemic administration of SC-236 as well
as its vehicle (100% dimethyl sulfoxide (DMSO)). The after-discharges of both
the WDR neurons and the simultaneously recorded SMUs after electrical stimuli
with 20 Hz were markedly depressed only by SC-236, indicating that the mechanisms
underlying the generation of the C-fiber mediated late responses and the after-discharges
may be different. The enhanced responsiveness of both WDR neurons and SMUs
to mechanical pressure stimuli (allodynia) and pinch stimuli (hyperalgesia)
in the BV experiments was apparently depressed by SC-236, but not its vehicle.
For electrical stimulation, the enhanced late responses and after-discharges,
but not early responses, of both the WDR neurons and the simultaneously recorded
SMUs were markedly depressed only by SC-236. This indicates that different
central pharmacological mechanisms underlie the generation of these enhanced
early, late responses, and after-discharges during BV-induced inflammation.
The data suggest that the COX-2 inhibitor SC-236 apparently depress the activities
of both spinal cord dorsal horn neuron and spinal withdrawal reflex during
BV-induced sensitization, indicating that COX-2 plays an important role in
the maintenance of central sensitization.
PMID: 14522004 [PubMed - indexed for MEDLINE]
| 10: Inflamm Res. 2003 Mar;52(3):132-9. |
Analysis of the
inflammatory response in the rat paw caused by the venom of Apis melifera
bee.
Calixto MC, Triches KM, Calixto JB.
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal
de Santa Catarina, Rua Ferreira Lima, 82, Florianopolis, SC, 88015-420, Brazil.
Calixto@farmaco.ufsc.br
OBJECTIVE: This study examines the pro-inflammatory action caused by subcutaneous
(
| 11: J Pharmacol Sci. 2003 Feb;91(2):95-104. |
Bee venom
induces apoptosis and inhibits expression of cyclooxygenase-2 mRNA in human
lung cancer cell line NCI-H1299.
Jang
MH, Shin
MC, Lim
S, Han
SM, Park
HJ, Shin
I, Lee
JS, Kim
KA, Kim
EH, Kim
CJ.
Department of Physiology,
To investigate whether bee venom (BV) induces apoptosis, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide assay, terminal deoxynucleotidyl transferase- mediated dUTP nick end-labeling
assay, 4,6-diamidino-2-phenylindole staining, flow cytometric analysis, and
DNA fragmentation assay were performed on NCI-H1299 lung cancer cells treated
with BV. Through morphological and biochemical analyses, it was demonstrated
that NCI-H1299 cells treated with BV exhibit several features of apoptosis.
In addition, reverse transcription-polymerase chain reaction and prostaglandin
E(2) (PGE(2)) immunoassay were performed to verify whether BV possesses an
inhibitory effect on the expression of cyclooxygenase (COX) and PGE(2 )synthesis.
Expression of COX-2 mRNA and synthesis of PGE(2) were inhibited by BV. These
results suggest the possibility that BV may exert an anti-tumor effect on
human lung cancer.
| 12: Chembiochem. 2002 Jul 2;3(7):664-71. |
Erratum in:
· Chembiochem. 2002 Aug 29;3(8):687.
Molecular basis
of phospholipase A2 inhibition by petrosaspongiolide M.
Dal Piaz F, Casapullo A,
Randazzo A, Riccio R, Pucci P, Marino G, Gomez-Paloma L.
Dipartimento di Chimica Organica e Biochimica Universita di Napoli Federico
II via Cinthia 6, 80126 Napoli, Italy.
Petrosaspongiolide M (PM) is
an anti-inflammatory marine metabolite that displays a potent inhibitory activity
toward group II and III secretory phospholipase A(2) (PLA(2)) enzymes. The
details of the mechanism, which leads to a covalent adduct between PLA(2)
and gamma-hydroxybutenolide-containing molecules such as PM, are still a matter
of debate. In this paper the covalent binding of PM to bee venom PLA(2) has
been investigated by mass spectrometry and molecular modeling. The mass increment
observed for the PM-PLA(2) adduct is consistent with the formation of a Schiff
base by reaction of a PLA(2) amino group with the hemiacetal function (masked
aldehyde) at the C-25 atom of the PM gamma-hydroxybutenolide ring. Proteolysis
of the modified PLA(2) by the endoprotease LysC followed by HPLC MS analysis
allowed us to establish that the PLA(2) alpha-amino terminal group of the
Ile-1 residue was the only covalent binding site for PM. The stoichiometry
of the reaction between PM and PLA(2) was also monitored and results showed
that even with excess inhibitor, the prevalent product is a 1:1 (inhibitor:enzyme)
adduct, although a 2:1 adduct is present as a minor component. The 2:1 adduct
was also characterized, which showed that the second site of reaction is located
at the epsilon -amino group of the Lys-85 residue. Similar results in terms
of the reaction profile, mass increments, and location of the PLA(2) binding
site were obtained for manoalide, a paradigm for irreversible PLA(2) inhibitors,
which suggests that the present results may be considered of more general
interest within the field of anti-inflammatory sesterterpenes that contain
the gamma-hydroxybutenolide pharmacophore. Finally, a 3D model, constrained
by the above experimental results, was obtained by docking the inhibitor molecule
into the PLA(2) binding site through AFFINITY calculations. The model provides
an interesting insight into the PM-PLA(2) inhibition process and may prove
useful in the design of new anti-inflammatory agents that target PLA(2) secretory
enzymes.
PMID: 12325001 [PubMed - indexed for MEDLINE]
| 13: Biol Pharm Bull. 2002 Jun;25(6):710-7. |
Participation
of the arachidonic acid cascade pathway in macrophage binding/uptake of oxidized
low density lipoprotein.
Beppu M, Watanabe M, Sunohara M, Ohishi K, Mishima E, Kawachi H, Fujii M, Kikugawa K.
Arachidonic acid cascade inhibitors, including phospholipase A2 inhibitors,
dexamethasone and quinacrine (mepacrine), cyclooxygenase inhibitors, indomethacin
and aspirin, and lipoxygenase inhibitor AA861, prevented foam cell formation
and cholesterol accumulation in the incubation of thioglycollate-induced mouse
peritoneal macrophages with oxidized low density lipoprotein (LDL) at 37 degrees
C for 24 h. These inhibitors similarly prevented foam cell formation of fibronectin-
and Ca ionophore A23187-stimulated macrophages. Binding and/or uptake of Dil
(1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine)-acetyl LDL by macrophages
at 37 degrees C for 3h and arachidonic acid release from macrophages at 37
degrees C for 4h were inhibited by dexamethasone. Exogenously added phospholipase
A2 of bee venom and Crotalus adamanteous venom increased arachidonic acid
release during incubation for 2 h, and increased macrophage binding and/or
uptake of Dil-acetyl LDL at 37 degrees C for 3 h, and foam cell formation
at 37 degrees C for 24 h. Protein kinase inhibitors, ML-9 and staurosporine,
that inhibited macrophage binding and/or uptake of Dil-acetyl LDL did not
inhibit arachidonic acid release, indicating that protein phosphorylation
was not involved in the arachidonic acid pathway in the macrophage scavenger
receptor activation. Nordihydroguaiaretic acid that inhibited arachidonic
acid release prevented binding and/or uptake of Dil-acetyl LDL. The release
of arachidonic acid was not enhanced by fibronectin-stimulation, indicating
that Ca influx-dependent stimulation of macrophage activity was not through
the activation of phospholipase A2. These results indicate that, as well as
the fibronectin-stimulated Ca influx pathway and protein phosphorylation pathway,
the arachidonic acid pathway participated in the activation of macrophages
to bind and take up oxidized LDL.
| 14: Life Sci. 2002 May 31;71(2):191-204. |
The water-soluble
fraction of bee venom produces antinociceptive and anti-inflammatory effects
on rheumatoid arthritis in rats.
Kwon YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Suwon, South Korea.
We recently demonstrated that bee venom (BV) injection into the Zusanli acupoint
produced a significantly more potent anti-inflammatory and antinociceptive
effect than injection into a non-acupoint in a Freund's adjuvant induced rheumatoid
arthritis (RA) model. However, the precise BV constituents responsible for
these antinociceptive and/or anti-inflammatory effects are not fully understood.
In order to investigate the possible role of the soluble fraction of BV in
producing the anti-arthritic actions of BV acupuncture, whole BV was extracted
into two fractions according to solubility (a water soluble fraction, BVA
and an ethylacetate soluble fraction, BVE) and the BVA fraction was further
tested.Subcutaneous BVA injection (0.9 mg/kg/day) into the Zusanli acupoint
was found to dramatically inhibit paw edema and radiological change (i.e.
new bone proliferation and soft tissue swelling) caused by Freund's adjuvant
injection. BVA treatment also reduced the increase in serum interleukin-6
caused by RA induction to levels observed in non-arthritic animals. In addition,
BVA therapy significantly reduced arthritis-induced nociceptive behaviors
(i.e. nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia).
Finally, BVA treatment significantly suppressed adjuvant-induced Fos expression
in the lumbar spinal cord at 3 weeks post-adjuvant injection. In contrast,
BVE treatment (0.05 mg/kg/day) failed to show any anti-inflammatory or antinociceptive
effects on RA.The results of the present study demonstrate that BVA is the
effective fraction of whole BV responsible for the antinociception and anti-inflammatory
effects of BV acupuncture treatment. Thus it is recommended that this fraction
of BV be used for long-term treatment of RA-induced pain and inflammation.
However, further study is necessary to clarify which constituents of the BVA
fraction are directly responsible for these anti-arthritis effects.
PMID: 12031688 [PubMed - indexed for MEDLINE]
| 15: Am J Chin Med. 2001;29(2):187-99. |
The analgesic
efficacy of bee venom acupuncture for knee osteoarthritis: a comparative study
with needle acupuncture.
Kwon YB, Kim JH, Yoon JH, Lee JD, Han HJ, Mar WC, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Suwon, Korea.
The aim of this investigation was to determine whether bee venom (BV) administered
directly into an acupoint was a clinically effective and safe method for relieving
the pain of patients with knee osteoarthritis (OA) as compared to traditional
needle acupuncture. We evaluated the efficacy of BV acupuncture using both
pain relief scores and computerized infrared thermography (IRT) following
4 weeks of BV acupuncture treatment. We observed that a significantly higher
proportion of subjects receiving BV acupuncture reported substantial pain
relief as compared with those receiving traditional needle acupuncture therapy.
Furthermore, the IRT score was significantly improved and paralleled the level
of pain relief.
Publication Types:
PMID: 11527062 [PubMed - indexed for MEDLINE]
| 16: Neurosci Lett. 2001 Aug 3;308(2):133-7. |
Visceral
antinociception produced by bee venom stimulation of the Zhongwan acupuncture
point in mice: role of alpha(2) adrenoceptors.
Kwon YB, Kang MS, Han HJ, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Suwon 441-744, South Korea.
The goal of the present study was to determine whether bee venom (BV) injection
into the Zhongwan acupoint (CV12), compared to injection into a non-acupoint,
produced antinociception in an acetic acid-induced visceral pain model. This
was accomplished by injecting BV subcutaneously into the Zhongwan acupoint
or into a non-acupoint 30 min before intraperitoneal injection of acetic acid
in ICR mice. BV injection into the acupoint produced a dose dependent suppression
of acetic acid-induced abdominal stretches and of acetic acid-induced Fos
expression in the spinal cord and the nucleus tractus solitarii. In contrast
BV injection into the non-acupoint only produced antinociception at the highest
dose of BV tested. Naloxone pretreatment did not alter the antinociceptive
effect of BV acupoint injection on the abdominal stretch reflex. On the other
hand, pretreatment with the alpha 2-adrenoceptor antagonist, yohimbine completely
blocked the antinociceptive effect of BV acupoint injection. These results
imply that BV acupoint stimulation can produce visceral antinociception that
is associated with activation of alpha 2-adrenoceptors, but not with naloxone-sensitive
opioid receptors.
PMID: 11457577 [PubMed - indexed for MEDLINE]
| 17: Acupunct Electrother Res. 2001;26(1-2):59-68. |
Antinociceptive
effects of bee venom acupuncture (apipuncture) in rodent animal models: a
comparative study of acupoint versus non-acupoint stimulation.
Kwon YB, Kang MS, Kim HW, Ham TW, Yim YK, Jeong SH, Park DS, Choi DY, Han HJ, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Suwon, South Korea.
From a clinical perspective, the alternative forms of acupoint stimulation
including electroacupuncture, moxibustion and acupressure appear to have more
potent analgesic effects than manual needle acupuncture. Bee venom (BV) injection
has also been reported to produce persistent nociceptive stimulation and to
cause neuronal activation in the spinal cord. In previous study, we observed
that BV stimulation into acupoint, namely BV acupuncture or Apipuncture, produced
more potent anti-inflammatory and antinociceptive potency in rodent arthritis
model as comparing with that of non-acupoint injection. Based on previous
report, we decided to further investigate that BV injection into an acupoint
produces antinociception as a result of its potent chemical stimulatory effect
in both abdominal stretch assay and formalin test. Different doses of BV were
injected into an acupoint or a non-acupoint 30 min prior to intraplantar formalin
injection or intraperitoneal acetic acid injection. Using the abdominal stretch
assay, we found that the high dose of BV (1:100 diluted in 20microl saline)
produced a potent antinociceptive effect irrespective of the site of BV injection.
In contrast the antinociceptive effect observed in both the writhing and formalin
tests following administration of a low dose of BV (1:1000 diluted in 20microl
saline) was significantly different between acupoint and non-acupoint sites.
BV injection into an acupoint (Zhongwan, Cv. 12) was found to produce significantly
greater antinociception than non-acupoint injection (
| 18: Neuropeptides. 2001 Feb;35(1):32-44. |
Differential
roles of spinal neurokinin 1/2 receptors in development of persistent spontaneous
nociception and hyperalgesia induced by subcutaneous bee venom injection in
the conscious rat.
Zheng
JH, Chen
J.
Department of Anatomy and K.K. Leung Brain Research Centre, The Fourth Military
Medical University, Xi'an, P.R. China.
To evaluate the roles of spinal neurokinin receptors in the development of
persistent nociception and hyperalgesia to thermal and mechanical stimuli
induced by subcutaneous (s.c.) bee venom injection, effects of intrathecal
(i.t.) pre- or post-treatment with a non-selective antagonist of (NK1/2) receptors,
[D-Arg1,D-Trp7,9,Leu11] substance P (spantide), and a selective NK3 receptor
antagonist, (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)-N-methyl
acetamide (SR142801) were assessed in conscious rat. Injection of bee venom
s.c. into the plantar surface of one hind paw resulted in a pathological pain
phenomenon characterized by a 1-2 h single phase of persistent spontaneous
nociceptive behaviors (continuously flinching the injected paw) and a 72-96
h profound primary thermal and mechanical hyperalgesia in the injection site
and a secondary thermal hyperalgesia in the non-injected hindpaw. Pre-treatment
with spantide i.t. at 0.05 microg, 0.5 microg and 5 microg produced a dose-related
suppression of the bee venom-induced flinching reflex during the whole time
course and the inhibitory rate was 24 +/- 12.60% (35.38 +/- 4.12 flinches/5
min, n=5), 48 +/- 6.75% (24.53 +/- 2.90 flinches/5 min, n=5) and 60 +/- 7.69%
(18.88 +/- 3.58 flinches/5 min, n=5) respectively when compared with the saline
control group (46.80 +/- 2.60 flinches/5 min, n=5). Post-treatment of spantide
i.t. at the highest dose (5 microg) used in the present study 5 min after
bee venom injection also produced a 49% suppression of the flinching reflex
in the control group [post-spantide vs saline: 19.42 +/- 3.15 (n=5) vs 38.42
+/- 3.25 flinches/5 min (n=5)]. Moreover, i.t. pre-treatment with 5 microg
spantide partially prevented the primary and secondary thermal hyperalgesia
from occurring, while it did not show any influence on the development of
primary mechanical hyperalgesia. Neither the established thermal nor mechanical
hyperalgesia identified in the above sites was affected by i.t. post-treatment
with the same dose of spantide 3 h after bee venom injection. Pre and post-treatment
of SR142801 did not produce any significant effect on the bee venom-induced
spontaneous pain and thermal and mechanical hyperalgesia. Our present result
suggests that activation of spinal NK1/2 receptors is involved in both induction
and maintenance of the persistent spontaneous nociception, while it is only
involved in induction of the primary and secondary thermal, but not primary
mechanical hyperalgesia induced by s.c. bee venom injection. The spinal NK3
receptor seems not likely to be involved in the bee venom-induced behavioral
response characterized by spontaneous pain and thermal and mechanical hyperalgesia.
Copyright 2001 Harcourt Publishers Ltd.
PMID: 11346308 [PubMed - indexed for MEDLINE]
| 19: J Vet Med Sci. 2001 Mar;63(3):251-9. |
Bee venom
pretreatment has both an antinociceptive and anti-inflammatory effect on carrageenan-induced
inflammation.
Lee JH, Kwon YB, Han HJ, Mar WC, Lee HJ, Yang IS, Beitz AJ, Kang SK.
Department of Veterinary Physiology,
College of Veterinary Medicine, Seoul National University, Suwon, South Korea.
Although the injection of bee venom (BV) has been reported to evoke tonic
pain and hyperalgesia, there is conflicting evidence in the literature indicating
that BV can also exert an anti-inflammatory and antinociceptive effects on
inflammation. In this regard, BV has been traditionally used in Oriental medicine
to relieve pain and to treat chronic inflammatory diseases such as rheumatoid
arthritis. The present study was designed to test the hypothesis that BV induces
acute nociception under normal conditions, but that it can serve as a potent
anti-inflammatory and antinociceptive agent in a localized inflammatory state.
The experiments were designed to evaluate the effect of BV pretreatment on
carrageenan (CR)-induced acute paw edema and thermal hyperalgesia. In addition,
spinal cord Fos expression induced by peripheral inflammation was quantitatively
analyzed. In normal animals subcutaneous BV injection into the hindlimb was
found to slightly increase Fos expression in the spinal cord without producing
detectable nociceptive behaviors or hyperalgesia. In contrast pretreatment
with BV (0.8 mg/kg) 30 min prior to CR injection suppressed both the paw edema
and thermal hyperalgesia evoked by CR. In addition, there was a positive correlation
between the percent change in paw volume and the expression of Fos positive
neurons in the spinal cord. These results indicate that BV pretreatment has
both antinociceptive and anti-inflammatory effects in CR-induced inflammatory
pain. These data also suggest that BV administration may be useful in the
treatment of the pain and edema associated with chronic inflammatory diseases.
PMID: 11307924 [PubMed - indexed for MEDLINE]
| 20: Pain. 2001 Feb 15;90(3):271-80. |
Bee venom
injection into an acupuncture point reduces arthritis associated edema and
nociceptive responses.
Kwon YB, Lee JD, Lee HJ, Han HJ, Mar WC, Kang SK, Beitz AJ, Lee JH.
Department of Veterinary Physiology,
College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul
National University, Suwon 441-744, South Korea.
Bee venom (BV) has traditionally been used in Oriental medicine to relieve
pain and to treat inflammatory diseases such as rheumatoid arthritis (RA).
While several investigators have evaluated the anti-inflammatory effect of
BV treatment, the anti-nociceptive effect of BV treatment on inflammatory
pain has not been examined. Previous studies in experimental animals suggest
that the therapeutic effect of BV on arthritis is dependent on the site of
administration. Because of this potential site specificity, the present study
was designed to evaluate the anti-nociceptive effect of BV injections into
a specific acupoint (Zusanli) compared to a non-acupoint in an animal model
of chronic arthritis.
| 21: Am J Emerg Med. 2000 Jan;18(1):22-7. |
Phospholipase A2-induced
coagulation abnormalities after bee sting.
Petroianu
G, Liu
J, Helfrich
U, Maleck
W, Rufer
R.
We will examine the correlation between various bee venom phospholipase A2
(PLA2) concentrations and several parameters of coagulation in human plasma
in order to offer a rationale for requesting a particular laboratory coagulation
test after bee sting(s). We will also evaluate in vitro the influence of clinically
available drugs with a noncompetitive inhibitory effect on PLA2 on the anticoagulant
effect of bee venom PLA2. Prothrombin index (PTi), partial thromboplastin
time (PTT), antithrombin III (AT III), soluble fibrin monomers (SFM), the
activity of coagulation factors I, II, V, and VIII, and thrombelastography
(TEG) parameters (split point [Sp], reaction time [R], kinetic time [K], coagulation
time [R + K], maximal amplitude [MA], and the growth angle [alpha]) were determined
before and after addition of 1.4, 2.7, and 4.1 units (1, 2, and 3 microg protein
respectively) of bee venom PLA2. Linear regression was used to determine the
significance of the relationship between these coagulation parameters and
bee venom PLA2 concentrations used. To study the influence of ketamine, lidocaine,
magnesium, furosemide, and cromolyn on the anticoagulant effect of bee venom
PLA2, PTi and factor II- and V-activities were measured before and after addition
of 2.7 units of PLA2 and PLA2 plus one of the tested substances. Determinations
of F II, PTi, F V, and F VIII showed a negative correlation to bee venom PLA2
concentration (r = -0.88, -0.86, -0.81, and -0.79 respectively). A positive
correlation was found for PTT (r = 0.69). FII- activity and PTi correlated
better with bee venom PLA2 concentration than other parameters. F I, AT III,
and SFM showed no changes. Whereas Sp, R, and K were prolonged by bee venom
PLA2 and a was reduced, there was no correlation to the PLA2 concentration.
Addition of none of the 5 substances could correct the effects of bee venom
PLA2 on the coagulation. In a patient with toxic reaction or a severe anaphylactic
reaction after bee sting(s) we suggest determinations of FII and/or PTi. This
will allow a quick and economical assessment of coagulation abnormalities
after bee sting(s). Noncompetitive PLA2-inhibitors (ketamine, lidocaine, magnesium,
furosemide, and cromolyn) are unable to correct in vitro the anticoagulant
effect of bee venom PLA2. They cannot be recommended at this stage for this
purpose. Further investigations with competitive PLA2-inhibitors are warranted.
PMID: 10674526 [PubMed - indexed for MEDLINE]
| 22: Neurosci Lett. 2000 Jan 7;278(1-2):41-4. |