Both acute and chronic pain are the most widespread medical issue strongly affecting people in terms of health
and quality of life. Unlike acute pain, chronic pain is a pathophysiological state arising from the alteration of the
peripheral and/or central nervous systems. It is frequently accompanied by the onset of hyperalgesia (increased
sensitivity to pain) and allodynia (painful sensation in response to usually innocuous stimuli). Pain is currently
treated with two major groups of analgesic drugs, namely non-steroidal anti-inflammatory drugs (NSAIDs) and
opioids; their use is associated with important side effects, which include gastrointestinal lesions [1] and
nephrotoxicity [2]; in the case of NSAIDs, respiratory depression, tolerance and physical dependence for opioids
[3]. For this reason, there is growing interest for the identification of alternative therapeutic strategies.
Curcumin (1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a yellow polyphenol,
diferuloylmethane, extracted from the rhizomes of turmeric (Curcuma longa)[4]. The therapeutic properties of
curcumin are well known indeed possesses low intrinsic toxicity along with a wide range of pharmacological
activities that include antitumor, anti-amyloid, antioxidant and anti-inflammatory capacities [5]. Antinociceptive
properties of curcumin have also been reported in preclinical studies [6], but its poor bioavaibility limits clinical
use as analgesic. Polymeric nanoparticle-based drug delivery is being increasingly investigated as a delivery
route able to overcome many obstacles associated with the delivery of free drugs. Recently, we investigated
the effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal
(i.t.) routes in several experimental models of pain [7]. We found that i.v. or i.t. routes of administration of
PLGA-CUR nanoformulations were effective in reducing the nociception induced by chemical stimuli or after the
ligation of the sciatic nerve in mice [7]. In the present study, putative antinociceptive effects induced by CUR
and PLGA-CUR after local subcutaneous administration was investigated in two animal models of pain i.e. the
formalin test and the hyperalgesia induced by zymosan. We found PLGA-CUR vesicles able to reduce
nociception induced by chemical stimuli, whereas CUR alone induced only a transient but not significant
antinociceptive effects. These results obtained after acute subcutaneous local PLGA-CUR vesicles
administration, further suggest that PLGA-CUR formulation should be developed as a new potential drug in the
treatment of pain in humans.
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1. M. Sinha, L. Gautam, P.K. Shukla et al., Mediators Inflamm., 2013, 258209.
2. M. Musu, G. Finco, R. Antonucci et al., Eur. Rev. Med. Pharmacol. Sci, 2011, 15, 1461.
3. R. Benyamin, A.M. Trescot, S. Datta et al., Pain Physician, 2018, S105.
4. S.C. Gupta, G. Kismali, B.B. Aggarwal, Biofactors, 2013, 39, 2.
5. S. Sharma, S.K. Kulkarni, J.N. Agrewala et al., Eur. J. Pharmacol., 2006, 536, 256.
6. L. Allegri, F. Rosignolo,C. Mio et al., J. Cancer Res. Clin. Oncol. 2018, 144, 285.
7. S. Pieretti, A.P. Ranjan, A. Di Giannuario et al., Colloids Surf B Biointerfaces, 2017, 158, 379
