Paraventricular oxytocinergic hypothalamic prevention or interruption of long-term potentiation in dorsal horn nociceptive neurons: Electrophysiological and behavioral evidence
Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, Querétaro, Mexico. Pain
(Impact Factor: 5.21).
07/2009; 144(3):320-8. DOI: 10.1016/j.pain.2009.05.002
Spinal long-term potentiation (LTP) elicited by noxious stimulation enhances the responsiveness of dorsal horn nociceptive neurons to their normal input, and may represent a key mechanism of central sensitization by which acute pain could turn into a chronic pain state. This study investigated the electrophysiological and behavioral consequences of the interactions between LTP and descending oxytocinergic antinociceptive mechanisms mediated by the hypothalamic paraventricular nucleus (PVN). PVN stimulation or intrathecal oxytocin (OT) reduced or prevented the ability of spinal LTP to facilitate selectively nociceptive-evoked responses of spinal wide dynamic range (WDR) neurons recorded in anesthetized rats. In a behavioral model developed to study the effects of spinal LTP on mechanical withdrawal thresholds in freely moving rats, the long-lasting LTP-mediated mechanical hyperalgesia was transiently interrupted or prevented by either PVN stimulation or intrathecal OT. LTP mediates long-lasting pain hypersensitivity that is strongly modulated by endogenous hypothalamic oxytocinergic descending controls.
Available from: Brendan Carvalho
- "More recently, animal studies have explored oxytocin's role in pain modulation. Intraventricular and intrathecal oxytocin in rat and mouse models has been shown to enhance antinociception     . The analgesic effect of oxytocin was diminished or absent in oxytocin knockout mice and with co-administration of oxytocin antagonists   . "
[Show abstract] [Hide abstract]
ABSTRACT: Oxytocin may play a role in pain modulation. The analgesic effects of breastfeeding with its associated endogenous oxytocin release have not been well investigated. To determine the impact of breastfeeding on incisional, perineal, and cramping pain after cesarean and vaginal delivery.DesignInstitutional review board–approved prospective observational study.SettingLabor and delivery and maternity wards.PatientsHealthy (American Society of Anesthesiology physical statuses 1 and 2) multiparous women who had cesarean (n = 40) and vaginal (n = 43) deliveries of singleton term infants and who were breastfeeding were enrolled.InterventionsWomen completed diaries to record incisional, perineal, or cramping pain scores 5 minutes before, during, and 5 minutes after breastfeeding.MeasurementsDemographic, obstetric, and neonatal variables, as well as analgesic use, were recorded.Main ResultsThere was no difference in incisional pain before, during, and after breastfeeding in women post–cesarean delivery. Cramping pain was significantly increased during, as compared with before or after breastfeeding in both the vaginal (P < .001) and cesarean (P < .001) delivery cohorts.Conclusions
There was no analgesic effect on incisional pain during breastfeeding, indicating that endogenous oxytocin associated with breastfeeding may not play a significant role in postpartum cesarean wound pain modulation. Breastfeeding increased cramping pain after vaginal and cesarean delivery. The increase in cramping pain is most likely due to the breastfeeding-associated oxytocin surge increasing uterine tone.
Available from: Abimael González-Hernández
- "No significant differences in PRL concentrations were observed between S and NS samples (n = 5). stimuli (DeLaTorre et al., 2009). The animals were not paralyzed, and we did not observe a withdrawal reaction during the experiments (Conde´s-Lara et al., 2012). "
[Show abstract] [Hide abstract]
ABSTRACT: Recently it has been suggested that the neurohormone PRL could act on the afferent nociceptive neurons. Indeed, PRL sensitizes TRPV1 channels present in nociceptive C-fibers and consequently reduces the pain threshold in a model of inflammatory pain. Accordingly, high plasma PRL levels in non-lactating females have been associated with several painful conditions (e.g. migraine). Paradoxically, an increase of PRL secretion during lactation induced a reduction in pain sensitivity. This difference could be attributed to the fact that PRL secreted from the adenopituitary (AP) is transformed into several molecular variants by the suckling stimulation. In order to test this hypothesis, the present study set out to investigate whether PRL from AP of suckled (S) or non-suckled (NS) lactating rats affects the activity of the male Wistar wide dynamic range (WDR) neurons. The WDR neurons are located in the dorsal horn of the spinal cord and receive input from the first-order neurons (Ab-, Ad- and C-fibers). Spinal administration of NS-PRL or S-PRL had no effect on the neuronal activity of non-nociceptive Ab-fibers. However, the activities of nociceptive Ad-fibers and C-fibers were: (i) increased by NS-PRL and (ii) diminished by S-PRL. Either NS-PRL or S-PRL enhanced the post-discharge activity. Taken together, these results suggest that PRL from S or NS lactating rats could either facilitate or depress the nociceptive responses of spinal dorsal horn cells, depending on the physiological state of the rats.
Available from: seas.upenn.edu
- "Of note, the identification of the duration threshold of 6.6 minutes in this study only considered the response of action potentials that were evoked early (10-40msec) after the electrical stimulus (Figure 6). The neurons associated with such action potentials are the myelinated A-fibers (DeLaTorre et al. 2009; Pezet et al. 2008; Yu et al. 2009), which have a lower electrical threshold for excitation than the unmyelinated C-fibers (Ramer et al. 2000). However, both fiber types have been shown to exhibit a uniform decrease in the amplitude of electricallyevoked compound action potentials in response to axonal stretch (Shi and Whitebone 2006), suggesting that the electrophysiologic results of the present study may extend to the unmyelinated C-fiber population. "
[Show abstract] [Hide abstract]
ABSTRACT: Cervical nerve roots are susceptible to compression injuries of various durations. The duration of an applied compression has been shown to contribute to both the onset of persistent pain and also the degree of spinal cellular and molecular responses related to nociception. This study investigated the relationship between peripherally-evoked activity in spinal cord neurons during a root compression and the resulting development of axonal damage. Electrically-evoked spikes were measured in the spinal cord as a function of time during and after (post-compression) a 15 minute compression of the C7 nerve root. Compression to the root significantly (p=0.035) reduced the number of spikes that were evoked over time relative to sham. The critical time for compression to maximally reduce evoked spikes was 6.6±3.0 minutes. A second study measured the post- compression evoked neuronal activity following compression applied for a shorter, sub-threshold time (three minutes). Ten minutes after compression was removed, the discharge rate remained significantly (p=0.018) less than baseline by 58±25% relative to sham after the 15 minute compression, but returned to within 3±33% of baseline after the three minute compression. Axonal damage was evident in the nerve root at day seven after nerve root compression only after a 15 minute compression. These studies demonstrate that even a transient mechanical insult to the nerve root is sufficient to induce sustained neuronal dysfunction and axonal pathology associated with pain, and results provide support that such minor neural tissue traumas can actually induce long-lasting functional deficits.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.