Highlights
- •Pre-emptive or perioperative IMT504 significantly reduce postsurgical pain
- •Pre-emptive IMT504 results in opioid-sparing effects
- •Pre-emptive IMT504 promotes an anti-inflammatory environment at the incision site and the spleen
- •IMT504 emerges as a potentially attractive drug for the control of postoperative pain
Abstract
Despite the available knowledge on underlying mechanisms and the development of several
therapeutic strategies, optimal management of postoperative pain remains challenging.
This pre-clinical study hypothesizes that, by promoting an anti-inflammatory scenario,
pre-emptive administration of IMT504, a non-coding, non-CpG oligodeoxynucleotide with
immune modulating properties, will reduce postincisional pain, also facilitating therapeutic
opioid-sparing. Male adult Sprague-Dawley rats with unilateral hindpaw skin-muscle
incision received pre-emptive (48 h and 24 h prior to surgery) or postoperative (6h
after surgery) subcutaneous vehicle (saline) or IMT504. Various groups of rats were
prepared for pain-like behaviour analyses, including subgroups receiving morphine
or naloxone, as well as for flow-cytometry or quantitative RT-PCR analyses of the
spleen and hindpaws (for analysis of inflammatory phenotype). Compared to vehicle-treated
rats, pre-emptive IMT504 significantly reduced mechanical allodynia by 6 h after surgery,
and accelerated recovery of basal responses from 72 h after surgery and onwards. Cold
allodynia was also reduced by IMT504. Postoperative administration of IMT504 resulted
in similar positive effects on pain-like behaviour. In IMT504-treated rats, 3 mg/kg
morphine resulted in comparable blockade of mechanical allodynia as observed in vehicle-treated
rats receiving 10 mg/kg morphine. IMT504 significantly increased hindpaw infiltration
of mesenchymal stem cells, CD4+T and B cells, and caused upregulated or downregulated
transcript expressions of interleukin-10 and interleukin-1β, respectively. Also, IMT504
treatment targeted the spleen, with upregulated or downregulated transcript expressions,
6 h after incision, of interleukin-10 and interleukin-1β, respectively. Altogether,
pre-emptive or postoperative IMT504 provides protection against postincisional pain,
through participation of significant immunomodulatory actions, and exhibiting opioid-sparing
effects.
Keywords
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Article info
Publication history
Accepted:
January 16,
2023
Received in revised form:
January 12,
2023
Received:
October 24,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc.
