Molecular biology of pain

Abstract

We have attempted to define some of the patterns of expression of the IEG Fos in pain-related states. On one level, Fos may be used simply as marker of afferent stimulation and disease state, and in this respect Fos activation may be a useful tool after nociceptive stimulation to examine the effectiveness of different analgesic regimens. For example, certain analgesics such as opioids, alpha 2 agonists and local anaesthetics are more effective when given pre-emptively or early in the injury rather than later on. Furthermore, the persistent expression of Fos in the presence of high dose pre-emptive opioids is disturbing and yet it may explain variable success of studies attempting to show pre-emptive analgesia with opioid-based analgesic regimens. We suggest that Fos expression, as well as defining the magnitude and the duration of insult to the spinal cord seems also to signal the adaptive responses of the nervous system to nociceptive insult. Though we have focused on only one IEG, c-fos, and attempted to relate appearance to known functional changes within the spinal cord, there are in fact many more genes known to be upregulated with the same or slower kinetics (e.g. Fos B, FRA-1, FRA-2, Jun B, Jun D, NGFI-A). Increased understanding of the role of these genes is likely to lead to many novel targets in the search for normalization or restoration of spinal cord function in pain states and after nerve injury.

Cetamina e analgesia preemptiva

“…Protoncogenes also activate transcription of Messenger RNAcontroller of protein synthesis, such as glutamate receptors (increasing their density in the membrane and making neuron more sensitive to this neurotransmitter), ion channels (increasing their excitability) and enzymes such as phosphorilases and proteinokinases. These changes are long-lasting and possibly permanent, making such neurons hypersensitive for long periods 70,73 . This way, ketamine may be important in central sensitization modulation.…”

“…Os protoncogenes também ativam a transcrição de RNA mensageiro controlador da síntese de proteínas, como receptores do glutamato (aumentando sua densidade na membrana e tornando o neurônio mais sensível a esse neurotransmissor), canais iônicos (aumentando a sua excitabilidade) e enzimas como fosforilases e proteinocinases. Essas mudanças são duradouras e eventualmente permanentes, tornando esses neurônios hipersensíveis por longos perío-dos 70,73 . Desta forma, a cetamina pode ser importante na modulação da sensibilização central.…”

“…Sua administração antes do estímulo doloroso teria, então, efeito preemptivo. 63,69,[73][74][75][76] . …”

Antinociceptive Effect of Amygdalin Isolated from <i>Prunus armeniaca</i> on Formalin-Induced Pain in Rats

“…10) The expression of an immediate-early gene, c-Fos in the spinal cord dorsal horn, is a marker of the neuronal activity that can be induced by noxious stimuli. [11][12][13][14][15] Therefore, it allows quantification of the effects of antinociceptive treatments and the identification their neuroanatomical localization. 13,16) Intraplantar formalin injection evokes c-Fos protein expression, principally in superficial (I-II) and deep (III-IV) dorsal horn laminae.…”

Peripheral and/or central effects of racemic‐, S(+)‐ and R(−)‐flurbiprofen on inflammatory nociceptive processes: a c‐Fos protein study in the rat spinal cord

“…Intraplantar carrageenan induces an in¯ammatory oedema (Winter et al, 1962;Di Rosa et al, 1971 and references therein) associated with mechanical allodynia (Kayser & Guilbaud, 1987), heat and mechanical hyperalgesia (Hargreaves et al, 1988;Iadarola et al, 1988;Joris et al, 1990 and the expression of c-Fos protein at the spinal cord level (Draisci & Iadarola, 1989;Noguchi et al, 1991Noguchi et al, , 1992 Honore et al, 1995). The expression of the nuclear protein c-Fos encoded by the immediate-early gene c-fos (for review see Morgan, 1991;Hughes & Dragunow, 1995;Morgan & Curran, 1995) is widely used as an indirect marker of neurons involved in spinal nociceptive processes (for review see Zieglgansberger & ToÈ lle, 1993;Munglani & Hunt, 1995;Chapman & Besson, 1997). Recently, in the carrageenan model of in¯ammatory nociception, we have demonstrated a signi®cant reduction of both the carrageenan-evoked oedema and spinal c-Fos protein expression by pre-treatment with various classical NSAIDs, such as indomethacin, aspirin, diclofenac, piroxicam, ketoprofen, ni¯umic acid and lornoxicam (see references in Buritova et al, 1996a;, and new NSAIDs acting against the inducible isoform of COX, such as selective COX-2 inhibitors (Buritova et al, 1996c).…”