3.4. Kappa opioid receptor blockade rescues inflammatory
pain-induced anxiety-like behaviours in female rats.
Previous data have shown that the blockade of the KOR/DYN signalling in
the NAc shell was an appropriate strategy to impair the development of
negative affect and alcohol-relapse-like behaviour induced by pain
(Massaly 2019, Lorente 2021). Thus, we found interesting to
pharmacologically analyse the role of NAc KOR in the inflammatory
pain-induced negative affective states reported in female rats in the
present study (figure 1). The blockade of the KOR locally in the nucleus
accumbens shell of female rats (figure 5A and S3A) impacted the
behaviour in the LDB without altering the SPT. In fact, in the case of
the SPT 48h, the ANOVA only detected differences for the time variable
(F(2,130)= 15.259; p= 0.0001; η2= 0.19) and the
interaction time x pain (F(2,130)= 11.576; p= 0.0001;
η2= 0.151). Further post-hoc analyses revealed that
CFA groups decreased their sucrose consumption compared with saline
groups at days 1-2 (p= 0.010), while no differences were found for the
other variables and interactions (Figure 4B) including the treatment
variable and its interactions (see table 1). The analysis of the SPT of
2h, revealed that the consumption of sucrose increases over the time and
the animals whose received NorBNI infusion showed a high sucrose
consumption than aCSF groups. Indeed, the ANOVA showed differences for
the time and treatment variables (F(2,130)= 51.364; p=0.0001;
η2= 0.597; and F(1,65)= 5.054; p= 0.028;
η2= 0.072). However, we did not detect differences for
pain variable and the interaction between variables (Figure 4C).
Finally, when analysing the LDB test we observed that NorBNI reverse the
decrease in the time spent in light box of CFA female rats without
altering the transition between boxes. For the time in light, we
detected differences in the time variable (F(1,65)= 12.969, p= 0.001;
η2= 0.166), showing that animals spent more time in
light during the second week. Furthermore, we detected differences in
the pain variable (F(1,65)= 11.470, p= 0.001; η2=
0.15) and in the interaction between pain x treatment (F(1,65)= 3.954,
p= 0.05; η2= 0.057). The treatment variable and the
other interactions showed no significative differences, and their F
values are showed in table 1. Post-hoc analyses of the significant
interaction and variables revealed that pain-suffering female rats that
received aCSF spent a shorter time in light box, compared to the
pain-free animals at 7 and 14 days (p7= 0.001,
p14= 0.012) while the pain-suffering female rats
receiving NorBNI spent in the light compartment the same time as saline
groups (Figure 4D, p7= 0.181; p14=
0.974). Thus, the administration of NorBNI counteracted the anxiety-like
behaviour induced by CFA injection in female rats. The analysis of the
transitions between boxes detected a significant effect for the time
(F(1,65)= 45.153; p= 0.0001) but not for the other variables and their
interactions (see table1). Thus, the transitions at 7 days were lower
than the transitions at 14 days either after saline or after CFA
injection.
Finally, we analysed the mechanical sensitivity thresholds with the VFT
to confirm that all CFA-treated rats maintained values until the end of
the protocol. We detected differences in pain (F(1,65)= 69.774; p=
0.0001; η2= 0.518) and time (F(1,65)= 55.861; p=
0.0001; η2= 0.521) variables and in the interaction
between time x pain (F(1,65)= 36.695); p= 0.0001; η2=
0.41), while no differences were detected for treatment variables and
for their interactions (see table 1). Post-hoc analyses revealed that
female rats showed lower paw withdrawal thresholds after 7 and 14 days
following CFA injection compared with their own basal values (before the
injection, p7= 0.0001); p14= 0.0001) and
with their saline counterparts (p7= 0.0001;
p14= 0.0001).