PMID- 36610589
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230129
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 796
DP  - 2023 Feb 6
TI  - Effects of intra-nasal melanocortin-4 receptor antagonist on trigeminal 
      neuropathic pain in male and female rats.
PG  - 137054
LID - S0304-3940(23)00008-3 [pii]
LID - 10.1016/j.neulet.2023.137054 [doi]
AB  - Treatment of chronic orofacial pain remains a major therapeutic challenge despite 
      available medications. Melanocortins have been implicated in pathologic pain. 
      Intrathecal administration of MC4R antagonists has been shown to alleviate 
      neuropathic pain (NP) in male rats. However, intrathecal delivery is very 
      invasive and requires surgeon's intervention. Intra-nasal rout offers a 
      non-invasive drug delivery method that can be self-administered making it very 
      attractive clinically. In this study, we investigated the effects of 
      intra-nasally delivered MC4R antagonist (HS014) on trigeminal neuropathic pain 
      (TNP) in male and female rats. We also measured the MC4R protein levels in the 
      trigeminal ganglia (TG) and infraorbital nerve (ION) of rats. We used ION chronic 
      constriction injury (ION-CCI) to induce TNP in rats. We used von Frey and 
      pinprick assays to measure the development of hypersensitivity in the face 
      following ION-CCI. At 22 days post-ION-CCI, we delivered HS014 intra-nasally to 
      measure its effects on TNP in rats. We used enzyme linked immunosorbent assay to 
      measure MC4R protein levels in the TG and ION. ION-CCI resulted in a significant 
      increase of MC4R protein levels in the ipsilateral TG and ION of male and female 
      rats. Intra-nasal delivered HS014 resulted in a significant reduction of ION-CCI 
      induced hypersensitivity in male and female rats. These results demonstrate that 
      intranasal delivery of MC4R antagonist alleviated TNP in male and female rats and 
      suggest that such treatment could be beneficial therapeutically for individuals 
      with chronic NP.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Korczeniewska, Olga Anna
AU  - Korczeniewska OA
AD  - Center for Orofacial Pain and Temporomandibular Disorders, Department of 
      Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA. 
      Electronic address: olga.korczeniewska@rutgers.edu.
FAU - Tatineni, Kalyani
AU  - Tatineni K
AD  - Center for Orofacial Pain and Temporomandibular Disorders, Department of 
      Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
FAU - Faheem, Shanzae
AU  - Faheem S
AD  - Center for Orofacial Pain and Temporomandibular Disorders, Department of 
      Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
FAU - Fresin, Wilner
AU  - Fresin W
AD  - Rutgers School of Graduate Studies, Newark Health Science Campus, Newark, NJ, 
      USA.
FAU - Bonitto, Jalen
AU  - Bonitto J
AD  - Center for Orofacial Pain and Temporomandibular Disorders, Department of 
      Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
FAU - Khan, Junad
AU  - Khan J
AD  - Eastman Institute for Oral Health, University of Rochester Medical Center, 
      Rochester, NY, USA.
FAU - Eliav, Eli
AU  - Eliav E
AD  - Eastman Institute for Oral Health, University of Rochester Medical Center, 
      Rochester, NY, USA.
FAU - Benoliel, Rafael
AU  - Benoliel R
AD  - Center for Orofacial Pain and Temporomandibular Disorders, Department of 
      Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA; Eastman 
      Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, 
      USA; Unit for Oral Medicine, Department of Oral and Maxillofacial Surgery, 
      Division of ENT, Head and Neck and Oral and Maxillofacial Surgery, Sourasky 
      Medical Center, Ichilov, Tel Aviv, Israel.
LA  - eng
PT  - Journal Article
DEP - 20230104
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Receptor, Melanocortin, Type 4)
SB  - IM
MH  - Female
MH  - Rats
MH  - Male
MH  - Animals
MH  - Hyperalgesia/drug therapy
MH  - Receptor, Melanocortin, Type 4
MH  - *Trigeminal Neuralgia/drug therapy/metabolism
MH  - *Neuralgia/drug therapy/metabolism
MH  - Facial Pain/drug therapy
OTO - NOTNLM
OT  - Ganglion
OT  - Intranasal
OT  - Melanocortin-4 receptor, Antagonist
OT  - Trigeminal neuropathic pain
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/01/08 06:00
MHDA- 2023/01/25 06:00
CRDT- 2023/01/07 19:14
PHST- 2022/11/27 00:00 [received]
PHST- 2022/12/29 00:00 [revised]
PHST- 2023/01/03 00:00 [accepted]
PHST- 2023/01/08 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2023/01/07 19:14 [entrez]
AID - S0304-3940(23)00008-3 [pii]
AID - 10.1016/j.neulet.2023.137054 [doi]
PST - ppublish
SO  - Neurosci Lett. 2023 Feb 6;796:137054. doi: 10.1016/j.neulet.2023.137054. Epub 
      2023 Jan 4.