Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were performed on awake rats. The pain threshold (tail flick latency, TFL) was measured with radiant heat tail-flick method. Microinjection of thyrotropin releasing hormone (TRH 2.5 micrograms/1 microliter) into septal area can increase remarkably and last 40 min, but the analgesic effect can not be reversed by the opioid receptor blocker naloxone (NAL) into the septal area; injection 10 micrograms of morphine into unilateral septal nucleus, the pain threshold had no obvious change; the after-effect of electroacupuncture (EA) was remarkably prolonged injecting TRH (1.5 micrograms) into unilateral septal nucleus. The after-effect of EA caused by TRH could abolish by NAL. The results imply that (1) microinjection of TRH into the unilateral septal nucleus could raise TFL, intraseptal opiate receptors may not be involved in analgesic effect elicited by TRH. (2) morphine was injection into unilateral septal nucleus having no effect on TFL, suggesting that endogenous opioid peptides in the septal nuclei might not be the major role in anti-nociceptive reaction in rats. (3) Microinjection TRH into the intraseptal can obviously prolong the after-effect of EA, NAL could abolish it, indicating that endogenous opiate peptides in the septal nuclei may play a role partially in mediating EA analgesia.
 ...
PMID:[The effects of microinjection of TRH or morphine into unilateral nucleus septum on pain threshold and electroacupuncture analgesia in rats]. 211 8

Using an antiserum (no. 373) raised against a tyrosinated analog of preproTRH53-74 [( Tyr1]preproTRH53-74 or pYT 22), we have demonstrated the presence of a discrete population of immunoreactive neurons in the midbrain periaqueductal gray (PAG). Relative to the distribution of serotonin, somatostatin, peptide histidine isoleucine (PHI), methionine enkephalin, substance P and neurotensin-containing neuronal perikarya in the PAG, neurons containing immunoreactive pYT 22 occupied a unique location in the ventrolateral PAG. In contrast, terminal fields containing these neuroactive substances with the exception of PHI, were seen in abundance in the region of the ventrolateral PAG neurons. These studies indicate that a non-TRH sequence contained within the N-terminal portion of the TRH prohormone are expressed in a distinct group of neurons in the ventrolateral PAG. The location of these neurons in the PAG in a region richly innervated by nerve terminals containing analgesia-mediating substances, suggests a possible role for proTRH-derived peptides in the modulation of nociception.
 ...
PMID:Neurons containing a N-terminal sequence of the TRH-prohormone (preproTRH53-74) are present in a unique location of the midbrain periaqueductal gray of the rat. 314 23

A tabular synopsis is presented for articles concerned with the effects of peptides on the central nervous system that appeared in the journal Peptides from 1980-1985. A table arranged alphabetically by peptide and one arranged by effects, both listing routes of injection, species, direction of change, and qualifying notes, provides easy cross-referencing of peptides and their effects. Over 80 peptides and over 135 effects are listed. The list of peptides includes, but is not limited to: ACTH, angiotensin, bombesin, bradykinin, calcitonin, casomorphin, CCK, ceruletide, CGRP, CRF, dermorphin, DSIP, dynorphin, endorphins, enkephalins, GRF, gastrin, LHRH, litorin, metkephamid, MIF-l, motilin, MSH, NPY, NT, oxytocin, ranatensin, sauvagine, substances P and K, somatostatin, TRH, VIP, vasopressin, and vasotocin. The list of effects includes, but is not limited to: aggression, alcohol, analgesia, attention, avoidance, behavior, cardiovascular regulation, catalepsy, conditioned behavior, convulsions, dopamine binding and metabolism, discrimination, drinking, EEG, exploration, feeding, fever, gastric secretion, GI motility, grooming, learning, locomotor behavior, mating, memory, neuronal activity, open field, operant behavior, rearing, respiration, satiety, scratching, seizure, sleep, stereotypy, temperature, thermoregulation and tolerance.
 ...
PMID:Central nervous system effects of peptides, 1980-1985: a cross-listing of peptides and their central actions from the first six years of the journal Peptides. 353 8

Nucleus Raphe Magnus (NRM) is a complex cell group. 5-HT, SP and ENK neurons in the NRM were identified by immunocytochemistry method. The afferent fibers containing 5-HT, SP, M-ENK, L-ENK, B-EP and SRIF were observed in NRM, the efferent fibers containing 5-HT, SP, ENK and TRH from NRM to spinal cord were studied. Two neurotransmitters (such as 5-HT with SP, ENK or TRH) were found in same neuron, fiber or vesicle. The neurons and axo-dendritic synapses of the NRM were analysed during Electroacupuncture (EA). The NRM increased their synaptic releases and the neurons were in active functional state during EA "Zusnanli". Studies show that NRM is one of important positions in EA analgesia.
 ...
PMID:[Relationship between acupuncture analgesia and neurotransmitters in nucleus raphe magnus]. 752 92

In summary, the effects of drugs affecting the MTD and abstinence syndrome in mice, rats, monkeys, and humans have been described. Although mu opioid antagonists block tolerance and dependence on morphine, they also antagonize the analgesic response to morphine and, therefore, may not be useful clinically in inhibiting the MTD process. On the other hand, delta-selective opioid antagonists do not modify morphine analgesia but block the MTD process and, therefore, may have therapeutic potential. Neuropeptides like TRH, MIF, and cyclo (Leu-Gly) appear to produce similar results although their mechanism of action may be quite different. Cyclo (Leu-Gly) produces its action on oral administration and, therefore, further studies are warranted with this peptide. The CCKB receptor antagonist enhances morphine analgesia and blocks tolerance to morphine but has no effect on the development of dependence on morphine. EAA antagonists like MK-801 block tolerance to the analgesic effect of morphine selectively but are quite toxic. Therefore, newer, less toxic agents like LY 274,614 need to be developed.
 ...
PMID:Drugs that modify opioid tolerance, physical dependence, and abstinence symptoms: preclinical and clinical studies. 874 81

High doses of GH, used to induce anabolism in prolonged critically ill patients, unexpectedly increased mortality. To further explore underlying mechanisms, a valid animal model is needed. Such a model is presented in this study. Seven days after arterial and venous cannulae placement, male New Zealand White rabbits were randomly allocated to a control or a critically ill group. To induce prolonged critical illness, a template controlled 15% deep dermal burn injury was imposed under combined general and regional (paravertebral) anesthesia. Subsequently, critically ill rabbits received supplemental analgesia and were parenterally fed with glucose, insulin, amino acids, and lipids. On d 1 and d 8 after randomization, acute and chronic spontaneous hormonal profiles of GH, TSH, and PRL secretion were obtained by sampling blood every 15 min for 7 h. Furthermore, GH, TSH, and PRL responses to an iv bolus of GH-releasing peptide 2 (GHRP-2) + TRH were documented on d 0, 1, and 8. Hemodynamic status and biochemical parameters were evaluated on d 0, 1, 3, 5, and 8, after which animals were killed and relative wet weight and water content of organs was determined. Compared with controls, critically ill animals exhibited transient metabolic acidosis on d 1 and weight loss, organ wasting, systolic hypertension, and pronounced anemia on d 8. On d 1, pulsatile GH secretion doubled in the critically ill animals compared with controls, and decreased again on d 8 in the presence of low plasma IGF-I concentrations from d 1 to d 8. GH responses to GHRP-2 + TRH were elevated on d 1 and increased further on d 8 in the critically ill animals. Mean TSH concentrations were identical in both groups on d 1 and 8, in the face of dramatically suppressed plasma T(4) and T(3) concentrations in the critically ill animals. PRL secretion was impaired in the critically ill animals exclusively on d 8. TSH and PRL responses to GHRP-2 and TRH were increased only on d 1. In conclusion, this rabbit model of acute and prolonged critical illness reveals several of the clinical, biochemical, and endocrine manifestations of the human counterpart.
 ...
PMID:A novel in vivo rabbit model of hypercatabolic critical illness reveals a biphasic neuroendocrine stress response. 1186 95

The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.
 ...
PMID:Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. 1237 95