Spinally administered dynorphin A produces long-lasting allodynia: involvement of NMDA but not opioid receptors.

The endogenous opioid peptide dynorphin A has non-opioid effects that can damage the spinal cord when given in high doses. Dynorphin has been shown to increase the receptive field size of spinal cord neurons and facilitate C-fiber-evoked reflexes. Furthermore, endogenous dynorphin levels increase following damage to the spinal cord, injury to peripheral nerves, or inflammation. In this study, sensory processing was characterized following a single, intrathecal injection of dynorphin A (1-17) in mice. A single intrathecal injection of dynorphin A (1-17) (3 nmol, i.t.) induced mechanical allodynia (hind paw, von Frey filaments) lasting 70 days, tactile allodynia (paint brush applied to flank) lasting 14 days, and cold allodynia (acetone applied to the dorsal hind paw) lasting 7 days. Similarly, dynorphin A (2-17) (3 nmol, i.t.), a non-opioid peptide, induced cold and tactile allodynia analogous to that induced by dynorphin A (1-17), indicating the importance of non-opioid receptors. Pretreatment with the NMDA antagonists, MK-801 and LY235959, but not the opioid antagonist, naloxone, blocked the induction of allodynia. Post-treatment with MK-801 only transiently blocked the dynorphin-induced allodynia, suggesting the NMDA receptors may be involved in the maintenance of allodynia as well as its induction. We have induced a long-lasting state of allodynia and hyperalgesia by a single intrathecal injection of dynorphin A (1-17) in mice. The allodynia induced by dynorphin required NMDA receptors rather than opioid receptors. This result is consistent with results in rats and with signs of clinically observed neuropathic pain. This effect of exogenously administered dynorphin raises the possibility that increased levels of endogenous dynorphins associated with spinal cord injuries may participate in the genesis and maintenance of neuropathic pain.

Single intrathecal injections of dynorphin A or des-Tyr-dynorphins produce long-lasting allodynia in rats: blockade by MK-801 but not naloxone.

Neuropathic pain states are accompanied by increased sensitivity to both noxious and non-noxious sensory stimuli, characterized as hyperalgesia and allodynia, respectively. In animal models of neuropathic pain, the presence of hyperalgesia and allodynia are accompanied by neuroplastic changes including increased spinal levels of substance P, cholecystokinin (CCK), and dynorphin. N-Methyl-D-aspartate (NMDA) receptors appear to be involved in maintaining the central sensitivity which contributes to neuropathic pain. In addition to its opioid activities, dynorphin has been suggested to act at the NMDA receptor complex. In an attempt to mimic the increased levels of spinal dynorphin seen in animal models of neuropathic pain, rats received a single intrathecal (i.t.) injection of dynorphin A(1-17), dynorphin A(1-13), dynorphin A(2-17) or dynorphin A(2-13) through indwelling catheters. Tactile allodynia was determined by measuring response threshold to probing with von Frey filaments. Dynorphin A(1-17) administration evoked significant and long-lasting tactile allodynia (i.e. > 60 days). Likewise, the i.t. administration of dynorphin A(1-13) or dynorphin A(2-17) or dynorphin A(2-13) also produced long-lasting tactile allodynia. Intrathecal pretreatment, but not post-treatment, with MK-801 prevented dynorphin A(1-17)-induced development of allodynia; i.t. administration of MK-801 alone had no effect on responses to tactile stimuli. In contrast, i.t. pretreatment with naloxone did not affect the development of tactile allodynia induced by dynorphin A(1-17) or alter sensory threshold when given alone. These results demonstrate that a single dose of dynorphin A, or its des-Tyr fragments, produces long-lasting allodynia which may be irreversible in the rat. Further, this effect appears to be mediated through activation of NMDA, rather than opioid, receptors. While the precise mechanisms underlying the development and maintenance of the allodynia is unclear, it seems possible that dynorphin may produce changes in the spinal cord, which may contribute to the development of signs reminiscent of a "neuropathic' state. Given that levels of dynorphin are elevated following nerve injury, it seems reasonable to speculate that dynorphin may have a pathologically relevant role in neuropathic pain states.

Orphanin-FQ/nociceptin: lack of anti nociceptive, hyperalgesic or allodynic effects in acute thermal or mechanical tests following intracerebroventricular or intrathecal administration to mice or rats.

A recent review calls attention to the discrepant results resulting from studies that have examined the nociceptive or antinociceptive properties of orphanin-FQ/nociceptin (Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-ArgLys-Leu-Ala-Asn-Gln; OFQ/N), the heptadecapeptide isolated from rat (nociceptin) and pig (orphanin FQ) brain that binds with high affinity to the opioid 'orphan' receptor (a seven transmembrane protein with sequence homology to opioid receptors), but exhibits only low affinity binding with conventional opioid ligands. Some of the discrepancy might result from differences in species, test, route of administration or time-course. We undertook a comprehensive examination of the effects of spinal (i.t.) or supraspinal (i.c.v.) administration of OFQ/N in mice and rats. Mice treated with OFQ/N either i.t. or i.c.v. demonstrated no significant nociceptive effect in the hot plate, warm-water or radiant heat tail-flick tests (except for the highest and most sedative dose of 10 nmol i.c.v. in the mouse warm-water tail-flick test). Pretreatment with the opioid antagonist naloxone or with peptidase inhibitors did not enhance the nociceptive effects of OFQ/N peptide in the warm-water tail-flick test. The motor activity in mice administered OFQ/N i.c.v. decreased significantly compared to controls. Rats administered i.c.v. or i.t. OFQ/N displayed no significant difference from vehicle-treated animals in similar noxious stimulus tests and OFQ/N-treated rats did not exhibit allodynia in a paw-withdrawal test. Overall, OFQ/N was ineffective in significantly altering response to noxious stimuli, regardless of whether the peptide was given at supraspinal or spinal sites in mice or in rats. In addition, i.c.v. or i.t. application of antisense or mismatch ODN to the orphan receptor did not modify tail-flick latency in either mice or rats, arguing against a tonic nociceptive tone mediated via the OFQ/N receptor.

Promotional timetables: an exploratory investigation of age norms for promotional expectations and their association with job well-being.

Using data representative of the U.S. working population, this research explores age norms for promotional expectations and assesses whether or not they carry with them psychological consequences. Findings reveal some degree of normativity in promotion expectations during two age brackets of the work life span, and they are consistent across assorted structural features. Normative expectations, however, were not associated with job well-being when other relevant factors were included in the analysis. Current job conditions were most clearly linked to well-being.

Fitting in: exploring the emotional dimension of adolescent peer pressure.

The general public and academic researchers alike have long recognized the importance of peer relations in the lives of young people. However, three issues are notably absent from the dominant models of peer influence. First, these models neglect the affective dimension of a youth's experiences. Second, the models tend to ascribe a passive role to the youth, a stance also reflected methodologically by the absence of the youth's voice. Third, the motivational component remains unspecified; that is, why does a youth conform to peer influence? Using a framework drawn from recent social psychological work on shame and related feelings, the present study collected qualitative data from twelve college students. The findings indicate that negative emotions play a role in peer influence, particularly feelings of inadequacy and isolation, as well as feeling ridiculed, all of which may be indicative of shame. Thus, shame-related feelings may be instrumental in motivating individuals to conform. A variety of directions for future research are suggested.

Effects of Hatha Yoga Practice on the Health-Related Aspects of Physical Fitness.

Ten healthy, untrained volunteers (nine females and one male), ranging in age from 18-27 years, were studied to determine the effects of hatha yoga practice on the health-related aspects of physical fitness, including muscular strength and endurance, flexibility, cardiorespiratory fitness, body composition, and pulmonary function. Subjects were required to attend a minimum of two yoga classes per week for a total of 8 weeks. Each yoga session consisted of 10 minutes of pranayamas (breath-control exercises), 15 minutes of dynamic warm-up exercises, 50 minutes of asanas (yoga postures), and 10 minutes of supine relaxation in savasana (corpse pose). The subjects were evaluated before and after the 8-week training program. Isokinetic muscular strength for elbow extension, elbow flexion, and knee extension increased by 31%, 19%, and 28% (p<0.05), respectively, whereas isometric muscular endurance for knee flexion increased 57% (p<0.01). Ankle flexibility, shoulder elevation, trunk extension, and trunk flexion increased by 13% (p<0.01), 155% (p<0.001), 188% (p<0.001), and 14% (p<0.05), respectively. Absolute and relative maximal oxygen uptake increased by 7% and 6%, respectively (p<0.01). These findings indicate that regular hatha yoga practice can elicit improvements in the health-related aspects of physical fitness. (c)2001 CHF, Inc.