FLARR Pages #23: Nahuatl Contributions to English and Spanish, Part I

Nahuatl is the language of the Aztecs, and other Central Mexican peoples. At the time of the Spanish conquest it was easily one of the most widely spoken native languages of the Americas, with a geographical extent from what is now the northern reaches of Mexico to the southern border of Nicaragua. It continues to be widely spoken in Mexico and ranks as the most common native language in that country, with approximately a million speakers. It is part of a larger language family called the Uto-Aztecan family that includes North American Indian languages such as Shoshone and Ute, spoken as far north as Montana

FLARR Pages #24: Nahuatl Contributions to English and Spanish, Part II

Nahuatl is the language of the Aztecs, and other Central Mexican peoples. At the time of the Spanish conquest it was easily one of the most widely spoken native languages of the Americas, with a geographical extent from what is now the northern reaches of Mexico to the southern border of Nicaragua. It continues to be widely spoken in Mexico and ranks as the most common native language in that country, with approximately a million speakers. It is part of a larger language family called the Uto-Aztecan family that includes North American Indian languages such as Shoshone and Ute, spoken as far north as Montana

Postnatal maturation of the spinal-bulbo-spinal loop: brainstem control of spinal nociception is independent of sensory input in neonatal rats

The rostroventral medial medulla (RVM) is part of a rapidly acting spino-bulbo-spinal loop that is activated by ascending nociceptive inputs and drives descending feedback modulation of spinal nociception. In the adult rat, the RVM can facilitate or inhibit dorsal horn neuron inputs but in young animals descending facilitation dominates. It is not known whether this early life facilitation is part of a feedback loop. We hypothesized that the newborn RVM functions independently of sensory input, before the maturation of feedback control. We show here that noxious hind paw pinch evokes no fos activation in the RVM or the periaqueductal gray at postnatal day (P) 4 or P8, indicating a lack of nociceptive input at these ages. Significant fos activation was evident at P12, P21, and in adults. Furthermore, direct excitation of RVM neurons with microinjection of DL-homocysteic acid did not alter the net activity of dorsal horn neurons at P10, suggesting an absence of glutamatergic drive, whereas the same injections caused significant facilitation at P21. In contrast, silencing RVM neurons at P8 with microinjection of lidocaine inhibited dorsal horn neuron activity, indicating a tonic descending spinal facilitation from the RVM at this age. The results support the hypothesis that early life descending facilitation of spinal nociception is independent of sensory input. Since it is not altered by RVM glutamatergic receptor activation, it is likely generated by spontaneous brainstem activity. Only later in postnatal life can this descending activity be modulated by ascending nociceptive inputs in a functional spinal-bulbo-spinal loop

The developmental emergence of differential brainstem serotonergic control of the sensory spinal cord

Descending connections from brainstem nuclei are known to exert powerful control of spinal nociception and pain behaviours in adult mammals. Here we present evidence that descending serotonergic fibres not only inhibit nociceptive activity, but also facilitate non-noxious tactile activity in the healthy adult rat spinal dorsal horn via activation of spinal 5-HT(3) receptors (5-HT(3)Rs). We further show that this differential serotonergic control in the adult emerges from a non-modality selective system in young rats. Serotonergic fibres exert background 5-HT(3)R mediated facilitation of both tactile and nociceptive spinal activity in the first three postnatal weeks. Thus, differential descending serotonergic control of spinal touch and pain processing emerges in late postnatal life to allow flexible and context-dependent brain control of somatosensation

What the young brain tells the spinal cord: top-down modulation of dorsal horn sensory circuitry during postnatal development

The brain can endogenously and powerfully modulate the processing of somatosensory information in the spinal cord. In adults, the rostroventral medulla (RVM) can inhibit and facilitate somatosensory processing in the adult dorsal horn, providing powerful control of pain behaviours. In neonates, balanced descending control of processing of dorsal horn activity is immature. Here, I examine the anatomical and functional maturation of descending control of spinal sensory circuitry in rats and hypothesise that descending serotonergic neurons in the RVM provide ongoing descending facilitation of spinal sensory networks in young animals. In chapter 2, I demonstrate that cutaneous noxious stimulation activates neurons in regions of the brainstem which receive sensory inputs from the dorsal horn at P4; eight days before noxious-evoked neuronal activation in descending modulatory nuclei. In chapter 3, silencing the RVM unmasked descending facilitation of nociceptive dorsal horn neuron electrophysiological activity in uninjured P8 and P21 rats, but unmasked descending facilitation at P40. Thus, there is a switch from ongoing descending facilitation to inhibition between P21 and P40. Experiments in chapter 4 demonstrate anatomical maturation of descending serotonergic pathways from the RVM to the spinal cord during postnatal development. In chapter 5, the function of these pathways was investigated. Here, deletion of descending serotonergic fibres or blockade of spinal 5-HT3Rs unmasked background serotonergic facilitation of tactile and noxious dorsal horn neuron electrophysiological activity at P8 and P21. In adults, 5-HT/5-HT3Rs also facilitate tactile inputs in the dorsal horn, but net modulation of noxious inputs switches to be inhibitory. In conclusion, a change in function of descending modulatory pathways arising from the brainstem occurs during postnatal development: in young rats, descending modulatory pathways enhance the saliency of low and high threshold mechanical inputs in the dorsal horn, whilst balanced inhibition and excitation of high and low threshold inputs occurs in adulthood

The consequences of pain in early life: injury-induced plasticity in developing pain pathways.

Pain in infancy influences pain reactivity in later life, but how and why this occurs is poorly understood. Here we review the evidence for developmental plasticity of nociceptive pathways in animal models and discuss the peripheral and central mechanisms that underlie this plasticity. Adults who have experienced neonatal injury display increased pain and injury-induced hyperalgesia in the affected region but mild injury can also induce widespread baseline hyposensitivity across the rest of the body surface, suggesting the involvement of several underlying mechanisms, depending upon the type of early life experience. Peripheral nerve sprouting and dorsal horn central sensitization, disinhibition and neuroimmune priming are discussed in relation to the increased pain and hyperalgesia, while altered descending pain control systems driven, in part, by changes in the stress/HPA axis are discussed in relation to the widespread hypoalgesia. Finally, it is proposed that the endocannabinoid system deserves further attention in the search for mechanisms underlying injury-induced changes in pain processing in infants and children

Targeting p38 Mitogen-activated Protein Kinase to Reduce the Impact of Neonatal Microglial Priming on Incision-induced Hyperalgesia in the Adult Rat

Neonatal surgical injury triggers developmentally regulated long-term changes that include enhanced hyperalgesia and spinal microglial reactivity after reinjury. To further evaluate priming of response by neonatal hindpaw incision, the authors investigated the functional role of spinal microglial p38 mitogen-activated protein kinase after reincision in adult rodents

The sensory coding of warm perception

Humans detect skin temperature changes that are perceived as warm or cool. Like humans, mice report forepaw skin warming with perceptual thresholds of less than 1°C and do not confuse warm with cool. We identify two populations of polymodal C-fibers that signal warm. Warm excites one population, whereas it suppresses the ongoing cool-driven firing of the other. In the absence of the thermosensitive TRPM2 or TRPV1 ion channels, warm perception was blunted, but not abolished. In addition, trpv1:trpa1:trpm3(-/-) triple-mutant mice that cannot sense noxious heat detected skin warming, albeit with reduced sensitivity. In contrast, loss or local pharmacological silencing of the cool-driven TRPM8 channel abolished the ability to detect warm. Our data are not reconcilable with a labeled line model for warm perception, with receptors firing only in response to warm stimuli, but instead support a conserved dual sensory model to unambiguously detect skin warming in vertebrates