A Pharmacological Review of Calcitonin Gene-Related Peptide Biologics and Future Use for Chronic Pain

Cooper, David A.; Laidig, William D.; Sappington, Alexandra; MacGregor, Gordon

doi:10.7759/cureus.35109

Cited by 4 publications

(4 citation statements)

References 56 publications

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“…In the present study, PNX + /nNOS-containing neurons formed the third largest (approximately 50%) population among all afferent cells capable of synthesizing and releasing PNX as their transmitter; the vast majority of these neurons belonged to Sl-and M-sized cells. This is well in line with data obtained in other species (human, rat, mouse, sheep, dromedary camel; [23,[54][55][56]) where nitrergic afferent neurons were found in an average of 40 additionally supports the hypothesis implied above, suggesting the existence of a PNX + /SP + /CGRP + /NOS + population of DRG cells.…”

Section: Discussionsupporting

confidence: 92%

“…Although the mechanism by which CGRP may potentiate the effects of SP is not fully clear, there is evidence that CGRP may delay the enzymatic degradation of SP [36,37]. CGRP has also been reported to increase the release of SP [38] as well as excitatory amino acid transmitters glutamate and aspartate [39] from central terminals of DRG neurons, possibly leading to strengthening the synaptic connections in the spinal dorsal horn, as well as increasing the effectiveness of these substances on the peripheral targets (for details, see [40]).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons

Mazur¹,

Lepiarczyk²,

Janikiewicz³

et al. 2023

Preprint

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Phoenixin-14 (PNX) - a bioactive peptide recently discovered in the rat brain, is highly conserved among many animal species: rodents (rat, mouse), pig, dog as well as humans. In rodents, PNX is expressed in areas responsible for the transmission of sensory information dorsal root ganglia (DRG) neurons, where it is present at relatively high levels and may preferentially suppress visceral pain. However, so far the presence of PNX has not been investigated in DRG in pigs, a species which, due to its anatomical and histological similarity to humans, is considered a better model for biomedical studies than rodents. The present study aimed to investigate the immunoreactivity of PNX in the DRG of the domestic pig. The collected spinal ganglia from the cervical (C), thoracic (Th), lumbar (L) and sacral (S) sections were transversely divided into serial sections of 10 μm thickness. DRG sections from each level of the spinal cord were double-labeled immunohistochemically using antibodies to PNX in a mixture with antibodies to: cocaine and amphetamine related transcript (CART), calretinin (CRT), calcytonin gene-related peptide (CGRP), galanin (GAL), nitric oxide synthase (nNOS), pituitary adenylate cyclase-acrivating polypeptide (PACAP), substance P (SP) or somatostatin (SOM), respectively. Immunohistochemical studies revealed PNX immunoreactivity in approximately 20% of nerve cells in all DRG examined, highlighting mainly the presence of the peptide in cells of small diameter (approximately 74% of all PNX-positive neurons found). Double labeling of DRG sections showed that PNX-immunopositive neurons stained also for CGRP (96.1%), SP (88.5%), nNOS (52.1%), GAL (20.7%), CRT (10.05%), PACAP (7.4%), CART (5.1%), or SOM (4.7%). Our research revealed for the first time the presence of the new peptide PNX in the sensory ganglia of the domestic pig, its co-localization with other important neurotransmitters involved in sensory transmission and its percentage distribution in ganglion domains. The exact function of PNX in DRG is not yet known, however, the high degree of co-localization of this peptide with the main nociceptive transmitters SP and CGRP may indicate its function in modulation of pain transmission.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons

Mazur¹,

Lepiarczyk²,

Janikiewicz³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Although the mechanism by which CGRP may potentiate the effects of SP is not fully clear, there is evidence that CGRP may delay the enzymatic degradation of SP [33,34]. CGRP has also been reported to increase the release of SP [35] as well as the excitatory amino acid transmitters glutamate and aspartate [36] from central terminals of DRG neurons, possibly leading to the strengthening of synaptic connections in the spinal dorsal horn, as well as increasing the effectiveness of these substances on the peripheral targets (for details, see [37]).…”

Section: Discussionmentioning

confidence: 99%

Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons

Mazur,

Lepiarczyk,

Janikiewicz

et al. 2023

IJMS

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Phoenixin-14 (PNX), initially discovered in the rat hypothalamus, was also detected in dorsal root ganglion (DRG) cells, where its involvement in the regulation of pain and/or itch sensation was suggested. However, there is a lack of data not only on its distribution in DRGs along individual segments of the spinal cord, but also on the pattern(s) of its co-occurrence with other sensory neurotransmitters. To fill the above-mentioned gap and expand our knowledge about the occurrence of PNX in mammalian species other than rodents, this study examined (i) the pattern(s) of PNX occurrence in DRG neurons of subsequent neuromeres along the porcine spinal cord, (ii) their intraganglionic distribution and (iii) the pattern(s) of PNX co-occurrence with other biologically active agents. PNX was found in approximately 20% of all nerve cells of each DRG examined; the largest subpopulation of PNX-positive (PNX+) cells were small-diameter neurons, accounting for 74% of all PNX-positive neurons found. PNX+ neurons also co-contained calcitonin gene-related peptide (CGRP; 96.1%), substance P (SP; 88.5%), nitric oxide synthase (nNOS; 52.1%), galanin (GAL; 20.7%), calretinin (CRT; 10%), pituitary adenylate cyclase-activating polypeptide (PACAP; 7.4%), cocaine and amphetamine related transcript (CART; 5.1%) or somatostatin (SOM; 4.7%). Although the exact function of PNX in DRGs is not yet known, the high degree of co-localization of this peptide with the main nociceptive transmitters SP and CGRP may suggests its function in modulation of pain transmission.

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“…Sodium-channel blockers are oral medications that may be used for acute pain, and phase 3 studies for the treatment of diabetic peripheral neuropathy are underway. The drawback to these agents is that they remain far in the future; realistically, it could be years before they can be used for chronic pain [33].…”

Section: Pain Management Through Other Psychedelicsmentioning

confidence: 99%

Answering Big Questions in Pain Medicine

Paladini¹,

Vallejo²,

Guerrero³

et al. 2023

Cureus

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The future of pain medicine is marked by many questions. What can other nations around the world learn from the opioid crisis that is still affecting the United States? The American opioid experience was mischaracterized and wrongly described, and its causes were misdiagnosed from the outset, leading to its mismanagement and the abandonment of many chronic pain patients to their suffering. There are a few new drugs in the analgesic armamentarium. What new targets do we have in pain medicine? There are many breakthroughs, discoveries, and potential new targets that could add to our analgesic prescribing choices. These include sigma receptors, d-amino acid oxidase, endoplasmic reticulum stress receptors, histone deacetylase, and others. Neuromodulation had been used with varying degrees of success for years, but with a simplistic approach based on the gate theory of pain. Despite our familiarity with neuromodulation and spinal cord stimulators, neuromodulation research indicates that the activation of glial cells may activate the immune system and enhance analgesia. Neuromodulation studies have concentrated on how electricity affects neuronal activity rather than how electrical activity could reduce pain. There are still more frontiers in our battle against pain and some promising avenues for treatments. This narrative review will try to summarize what can be done from the perspective of recent technological and pharmacological developments.

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A Pharmacological Review of Calcitonin Gene-Related Peptide Biologics and Future Use for Chronic Pain

Cited by 4 publications

References 56 publications

Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons

Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons

Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons

Answering Big Questions in Pain Medicine

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