H .-X. Liu, T. Hokfelt Brain Research 886 2000 67 –72
69
point. A P value less than 0.05 was chosen as the significant level.
3. Results
The data for galanin and saline in allodynic rats, and saline in non-allodynic rats were combined from the blind
and non-blind series, since no differences were noted. The data for M35 in non-allodynic rats were blind. The rest of
the data was non-blind.
3.1. Anti-allodynic effect of galanin in allodynic rats The effect of i.t. galanin or M35 on the behavioral
thresholds for withdrawal of the hindpaw ipsilateral to the nerve injury was determined in allodynic rats. The results
are shown as Fig. 1A and Table 1. Neither vehicle, nor M35, nor high dose M35 treatment had any significant
effect on the mechanical threshold compared with baseline Friedman ANOVA, P.0.05, whereas the threshold in-
creased dose-dependently after i.t. injection of galanin P,0.001. Galanin-treated rats had a significant increase
in mechanical thresholds at 30 min after the last injection compared with saline and M35 groups Kruskal–Wallis
ANOVA, P,0.01.
3.2. M35-induced allodynia in non-allodynic model rats In non-allodynic rats with the same nerve injury opera-
Fig. 1. Effects of galanin and M35 on mechanical threshold in allodynic
tion, M35,
galanin, bradykinin
or its
fragment
A and non-allodynic B rats. Galanin or M35 was given in a
bradykinin2–9 were applied. M35 induced a dramatic
cumulative regime of 1, 9, 20 mg, totally 30 mg and 0.1, 0.2, 0.7 mg,
dose-dependent drop of the mechanical threshold Fried-
totally 1 mg, respectively. In allodynic rats galanin dose-dependently induced a significant increase of mechanical threshold repeated measures
man ANOVA, P,0.0001, while no significant changes
ANOVA on ranks, P,0.001, neither M35 nor saline had any effect
were observed for galanin, bradykinin, bradykinin2–9 or
repeated measures ANOVA on ranks, P50.80, P50.18 respectively. In
saline P.0.05 Fig. 1B; Table 1. The mechanical
non-allodynic rats, M35 induced a dramatic drop of the mechanical
threshold was lower than in the other groups at 30 min
threshold P,0.0001 which did not change after injection of galanin or
after 0.2 mg M35 and at 15 min, 30 min, 60 min after 0.7
saline P50.22, P50.57, respectively. , indicate P,0.05, P,0.01 compared among groups at the same time point one-way ANOVA on
mg M35 injection Kruskal–Wallis ANOVA, P,0.001,
ranks. The arrows indicate that i.t. injection was given immediately after
P,0.001, P,0.01, P,0.05 respectively.
the measurement of the value at the time point.
In view of a bradykinin fragment being part of the M35
Table 1
a
Effects of high dose M35 on mechanical threshold in allodynic and of bradykinin, and bradykinin fragment2–9 in non-allodynic rats
Group Drug
Time minutes after i.t. injection Friedman
ANOVA ↓
15 30
↓ 45
60 ↓
75 90
120 150
180 Allodynic rats
High dose M35
2.8560.78 2.8560.78
2.8560.39 2.8561.04
2.8561.43 2.8561.43
2.8560.39 2.8560.26
2.8560.78 2.8560.0
P50.55 Non-allodynic rats
Bradykinin 13.560.0
13.562.38 13.561.0
13.560.0 13.560.78
13.561.0 13.561.38
13.561.78 13.561.78
11.1562.78 P50.46
Bradykinin2–9 13.560.78
13.561.38 13.561.38
13.561.78 13.561.0
13.562.78 13.561.78
13.560.78 13.562.78
13.561.0 P50.52
a
The numerals in the table are median6median-derived absolute deviation MAD. No changes were observed in each group repeated measures ANOVA on ranks. P.0.05. The arrows indicate that i.t. injection was given immediately after the measurement of the value at the time point.
70 H
molecule, a high dose 10 mg of bradykinin or its ng–1 mg increased reflex excitability. It has also been
fragment was injected in non-allodynic rats. All five rats reported that in normal rats a single i.t. injection of galanin
receiving this dose of bradykinin started to struggle in the 0.1 and 1 nmol decreases the nociceptive threshold for
domes within 1 min and this behavior lasted for about 1 mechanical stimulation [18]. Recently Kerr et al. [15]
min. No behavioral response was observed in the four rats found that following full sciatic transection or partial nerve
that received 10 mg of bradykinin2–9. injury, spontaneous and evoked neuropathic pain behaviors
are largely eliminated or severely compromised in galanin null mutant mice. Furthermore, chronic intrathecal delivery
4. Discussion of low dose 25 ng h, 14 d exogenous galanin to nerve-
