Prolactin Regulates Pain Responses Via a Female-Selective Nociceptor-Specific Mechanism

Patil, Mayur; Belugin, Sergei; Mecklenburg, Jennifer; Wangzhou, Andi; Paige, Chandler; Barba-Escobedo, Priscilla A.; Boyd, Jacob T.; Goffin, Vincent; Grattan, David R.; Boehm, Ulrich; Dussor, Gregory; Price, Theodore J.; Akopian, Armen N.

doi:10.2139/ssrn.3403333

Cited by 13 publications

(28 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This area of research has not garnered much attention but may be important for neuronal function given the key role of translation regulation in synaptic plasticity (80). In the context of pain, we recently demonstrated that female-selective translation of the prolactin receptor mRNA in nociceptors is a causative factor in the pain promoting effects of prolactin in female mice (18).…”

Section: Discussionmentioning

confidence: 99%

“…However, transcription and translation are not directly coupled in eukaryotes, so there can be important divergences between transcriptomes (the cellular RNA profile) and translatomes (the subset of the transcriptome that is bound to ribosomes for translation) in cells (17). An example in nociceptors is the similar transcription of the prolactin receptor (Prlr) in male and female nociceptors, but the female-selective localized translation of the Prlr mRNA (18). This sex difference in Prlr mRNA translation causes an important sex difference in prolactin-evoked pain responses (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

“…An example in nociceptors is the similar transcription of the prolactin receptor (Prlr) in male and female nociceptors, but the female-selective localized translation of the Prlr mRNA (18). This sex difference in Prlr mRNA translation causes an important sex difference in prolactin-evoked pain responses (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Tavares‐Ferreira

Ray

Sankaranarayanan

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: There are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences. Methods: We used Translating Ribosome Affinity Purification (TRAP) sequencing and behavioral pharmacology to test the hypothesis that nociceptor (Nav1.8 expressing neurons) translatomes would differ by sex. Results: We found 66 genes whose mRNA were sex-differentially bound to nociceptor ribosomes. Many of these genes have known neuronal functions but have not been explored in sex differences in pain. We focused on Ptgds, which was increased in female mice. The mRNA encodes the prostaglandin D2 (PGD2) synthesizing enzyme. We observed increased Ptgds protein and PGD2 in female mouse DRG. The Ptgds inhibitor AT-56 caused intense pain behaviors in male mice but was only effective at high doses in females. Conversely, female mice responded more robustly to another major prostaglandin, PGE2, than did male mice. Ptgds protein expression was also higher in female cortical neurons, suggesting DRG findings may be generalizable to other nervous system structures. Conclusions: Nociceptor TRAP sequencing (TRAP-seq) reveals unexpected sex differences in one of the oldest known nociceptive signaling molecule families, the prostaglandins. Our results demonstrate that translatome analysis reveals physiologically relevant sex differences important for fundamental protective behaviors driven by nociceptors.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Tavares‐Ferreira

Ray

Sankaranarayanan

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…[57][58][59] These effects are sex-dependent, with prolactin appearing to only regulate nociception in female and not male rodents. [59][60][61] In male rats, prolactin-induced TIDA neurone activation is postsynaptic because it endures in the presence of the voltage-gated Na + channel antagonist, tetrodotoxin. 22 The response is characterised by a mixed-cationic current, mediated via transient receptor potential (TRP) channels, possibly one of the TRPC channels.…”

Section: Discussionmentioning

confidence: 99%

Acute effects of prolactin on hypothalamic prolactin receptor expressing neurones in the mouse

Georgescu

Ladyman

Brown

et al. 2020

J Neuroendocrinology

View full text Add to dashboard Cite

In addition to its critical role in lactation, the anterior pituitary hormone prolactin also influences a broad range of other physiological processes. In particular, widespread expression of prolactin receptor (Prlr) in the brain has highlighted pleiotropic roles for prolactin in regulating neuronal function, including maternal behaviour, reproduction and energy balance. Research into the central actions of prolactin has predominately focused on effects on gene transcription via the canonical JAK2/STAT5; however, it is evident that prolactin can exert rapid actions to stimulate activity in specific populations of neurones. We aimed to investigate how widespread these rapid actions of prolactin are in regions of the brain with large populations of prolactin-sensitive neurones, and whether physiological state alters these responses. Using transgenic mice

show abstract

“…The main downstream effector pathway of prolactin/prolactin receptor signaling is the JAK/STAT pathway, and MAPK is also activated [ 502 ]. Nevertheless, the prolactin receptor is intriguing in the context of nociception due to its prolactin-dependent sensitization predominantly in females, which also worked in isolated sensory neurons of females [ 503 , 504 ]. More specifically, it has been hypothesized that the female sex hormone estradiol regulates translation of prolactin receptor mRNA.…”

Section: Effects Predominantly or Exclusively On Sensory Neuronsmentioning

confidence: 99%

Novel Analgesics with Peripheral Targets

Ciotu

Fischer

2020

Neurotherapeutics

View full text Add to dashboard Cite

A limited number of peripheral targets generate pain. Inflammatory mediators can sensitize these. The review addresses targets acting exclusively or predominantly on sensory neurons, mediators involved in inflammation targeting sensory neurons, and mediators involved in a more general inflammatory process, of which an analgesic effect secondary to an anti-inflammatory effect can be expected. Different approaches to address these systems are discussed, including scavenging proinflammatory mediators, applying anti-inflammatory mediators, and inhibiting proinflammatory or facilitating anti-inflammatory receptors. New approaches are contrasted to established ones; the current stage of progress is mentioned, in particular considering whether there is data from a molecular and cellular level, from animals, or from human trials, including an early stage after a market release. An overview of publication activity is presented, considering a IuPhar/BPS-curated list of targets with restriction to pain-related publications, which was also used to identify topics.

show abstract

Prolactin Regulates Pain Responses Via a Female-Selective Nociceptor-Specific Mechanism

Cited by 13 publications

References 0 publications

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice

Acute effects of prolactin on hypothalamic prolactin receptor expressing neurones in the mouse

Novel Analgesics with Peripheral Targets

Contact Info

Product

Resources

About