Biomedical subjects

N Altier

Publications and source records attributed to N Altier.

10 recordsLinked to original sources

PubMed2002

Long-term adjustment in burn victims: a matched-control study.

BACKGROUND: To date, there is little information about how severely burned patients compare to unburned healthy individuals in terms of psychological profile and quality of life. As part of a larger study on the sensory consequences of burns, we assessed psychological functioning and quality of life in burned patients and unburned healthy control subjects. We also examined whether burn patients experiencing pain and/or paresthetic sensations (i.e. symptomatic patients) present a profile that is different from those who are asymptomatic. METHODS: Forty-nine burned patients (% total body surface area = 34 59 % +/- 13.40; 82% males/18% females) were evaluated 63 59 +/- 28.1 months post-burn. They were matched with 49 unburned healthy volunteers on age, sex, and education level. All subjects were administered the Symptom Checklist 90-Revised (SCL-90-R) to assess psychological functioning and the 36-item Short-Form Health Survey (SF-36) to assess quality of life. RESULTS: Approximately 25% of the burn patients presented clinically-significant psychological disturbances compared to 12% in the control group. Burn patients enjoyed a quality of life comparable to that of the control subjects, although they perceived some deterioration in their general health. More symptomatic than asymptomatic patients suffered from clinically-relevant somatization and obsessive-compulsive disturbances. CONCLUSIONS: Severely burned patients adjust relatively well, although some develop clinically-significant psychological disturbances such as somatization and phobic anxiety. Burn patients experiencing abnormal sensations in their healed wounds (i.e. symptomatic patients) do not suffer from maladjustment to a greater extent than their asymptomatic counterparts, although more symptomatic patients experience somatization and obsessive-compulsive behaviours.

Adaptation, Psychological↗

PubMed2001

Successful use of methadone in the treatment of chronic neuropathic pain arising from burn injuries: a case-study.

Methadone is used increasingly as a second-line opioid in the management of cancer pain refractory to conventional opioids. Recent case studies suggest that its use as an analgesic could be extended to non-cancer pain, especially neuropathic pain. The present case study reports, for the first time, the efficacy of methadone in a burn patient experiencing neuropathic pain in his healed wounds. The patient sustained extensive (55% total body surface area) chemical burns and developed chronic burning sensations, particularly in the lower limbs where skin grafting had been performed. Conventional pharmacotherapies against neuropathic pain were attempted to control pain for over 5 years. The agents used included long- and short-acting opioids, amitriptyline, clonazepam, and gabapentin, but they all failed to relieve the pain. When methadone (5 mg every 12 h) was introduced, it significantly alleviated the patient's pain within a few days of administration. The patient has now been taking methadone (15 mg every 12 h) for 10 months and reports that the opioid caused 70% pain relief and a 55% amelioration in his quality of life. Although these results are based on a case report, they suggest that a switch to methadone might be useful in some burn patients who have developed chronic neuropathic pain unrelieved by conventional pharmacotherapies. Methadone, however, needs to be titrated with vigilance and thus should be administered by a physician experienced with its use in the treatment of chronic pain.

Analgesics, Opioid↗

PubMed2000

Neuropeptide FF attenuates allodynia in models of chronic inflammation and neuropathy following intrathecal or intracerebroventricular administration.

Experiments were conducted to explore the effects of Neuropeptide FF acting at spinal and supraspinal sites in models of chronic inflammatory or neuropathic pain and of acute pain. Neuropeptide FF was administered intrathecally (i.t.; 10.0, 25.0 and 50.0 nmol) or intracerebroventricularly (i.c.v.; 10.0, 12.5 and 15.0 nmol) either 24 h after inflammation-inducing injections of Freund's Complete Adjuvant in one hind paw or 7 days after unilateral sciatic nerve constriction. Evoked pain was assessed by measuring the withdrawal response threshold (in grams of pressure) to a mechanical stimulus applied to the plantar surface of the injured paw. Neuropeptide FF dose-dependently attenuated the allodynic response (i.e., withdrawal from a normally innocuous stimulus) to mechanical stimulation in the inflammatory and neuropathic model following i.t. (ED50=20.86 nmol and ED50=18.91 nmol, respectively) and i.c.v. (ED50=12.31 nmol and ED50=11.68 nmol, respectively) administration. Pretreatment with naloxone (2.0 mg/kg; s.c.) attenuated the anti-allodynic effect of i.t. or i.c.v. Neuropeptide FF in rats experiencing inflammatory, but not neuropathic pain. In contrast, Neuropeptide FF administered i.t. (10.0, 25.0 and 50.0 nmol) or i.c.v. (10.0, 12.5 and 15.0 nmol) had no effect on the response to acute thermal or mechanical stimulation. Neuropeptide FF injected i.t. or i.c.v. in inflamed or neuropathic rats did not produce any sign of motor dysfunction. These results suggest that Neuropeptide FF acting at spinal and supraspinal sites plays a role in modulating chronic, but not acute pain. Furthermore, the results suggest that the anti-allodynic effect of Neuropeptide FF is mediated indirectly by naloxone-sensitive opioid mechanisms in rats subjected to inflammatory, but not neuropathic pain.

Animals↗

PubMed1999

The role of dopamine in the nucleus accumbens in analgesia.

Opioid and psychostimulant drugs have long been used for the relief of chronic pain in the clinical situation. Animal studies confirm that these drugs alleviate persistent or tonic pain. Little is known, however, about the neural systems underlying the suppression of tonic pain except that they are different from those mediating the suppression of phasic (i.e., sharp and short-lasting) pain. Although spinal and brainstem-descending pain suppression mechanisms play a role in mediating the inhibition of tonic pain, it appears that this response is additionally mediated by the activation of mechanisms lying rostral to the brainstem. Recent studies suggest that the activation of mesolimbic dopamine (DA) neurons, arising from the cell bodies of the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAcc), plays an important role in mediating the suppression of tonic pain. Other studies suggest that this pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, through the endogenous release of opioids and substance P (SP) in the midbrain.

Analgesics, Opioid↗

PubMed1999

The tachykinin NK-1 receptor antagonist, RP-67580, infused into the ventral tegmental area prevents stress-induced analgesia in the formalin test.

Substance P (SP) receptors in the ventral tegmental area (VTA) play a critical role in mediating the stress-induced activation of midbrain ascending dopamine (DA) neurons. Interestingly, SP acting in the VTA induces analgesia in the formalin test for tonic pain. Because exposure to stress inhibits pain in this test, we speculated that SP receptors in the VTA might mediate stress-induced analgesia. The present study explored this idea by examining the effect of blocking tachykinin NK-1 receptors in the VTA on footshock stress-induced analgesia in the formalin test. Intra-VTA infusions of the novel tachykinin NK-1 receptor antagonist, RP-67580, prevented this response. This finding suggests that exposure to stress inhibits tonic pain through the release of endogenous SP in the VTA.

Analgesics↗

PubMed1998

Dopamine receptor antagonists in the nucleus accumbens attenuate analgesia induced by ventral tegmental area substance P or morphine and by nucleus accumbens amphetamine.

In the present study, we examined the effects of dopamine (DA) receptor antagonists infused into the nucleus accumbens septi (NAS) on analgesia induced by intra-ventral tegmental area (VTA) infusions of the substance P (SP) analog, DiMe-C7 or morphine and intra-NAS infusions of amphetamine. Rats received intra-NAS infusions of either the mixed DA receptor antagonist flupenthixol (1.5 or 3.0 microg/0.5 microl/side; DiMe-C7 only), the DA D1/D5 receptor antagonist SCH 23390 (0.1 microg/0.5 microl/side; DiMe-C7 only) or the DA D2-type receptor antagonist raclopride (1.0, 3.0 or 5.0 microg/0.5 microl/side). Ten minutes later, rats received intra-VTA infusions of DiMe-C7 (3.0 microg/0.5 microl/side) or morphine (3.0 microg/0.5 microl/side) or intra-NAS infusions of amphetamine (2.5 microg/0.5 microl/side). Animals were then administered the formalin test for tonic pain. Intra-NAS raclopride prevented analgesia induced by intra-VTA DiMe-C7, intra-VTA morphine and intra-NAS amphetamine. Similarly, intra-NAS flupenthixol or SCH 23390 attenuated the analgesia induced by intra-VTA DiMe-C7. These findings suggest that tonic pain is inhibited, at least in part, by enhanced DA released from terminals of mesolimbic neurons. Furthermore, the evidence that SP and opioids in the VTA mediate stress-induced analgesia suggests that the pain-suppression system involving the activation of mesolimbic DA neurons is naturally triggered by exposure to stress, pain or both.

Adrenergic Antagonists↗

PubMed1997

Neuropeptide FF in the VTA blocks the analgesic effects of both intra-VTA morphine and exposure to stress.

It has been shown previously that i.c.v. administration of neuropeptide FF (NPFF) attenuates the analgesic effects of exogeneous and endogeneous opioids. Here, we report that intra-ventral tegmental area (VTA) NPFF pre-treatment blocks the analgesia induced by either intra-VTA morphine or exposure to footshock stress in the formalin test for tonic pain. These findings suggest that NPFF in the VTA may play an adaptive role in regulating the response to stress.

Analgesics, Opioid↗

PubMed1997

Tachykinin NK-1 and NK-3 selective agonists induce analgesia in the formalin test for tonic pain following intra-VTA or intra-accumbens microinfusions.

Experiments were designed to examine the analgesic effects induced by selective tachykinin receptor agonists microinfused into either the ventral tegmental area (VTA) or nucleus accumbens septi (NAS). Rats were tested in the formalin test for tonic pain following an injection of 0.05 ml of 2.5% formalin into one hind paw immediately after bilateral intra-VTA infusions of either the NK-1 agonist, GR-73632 (0.005, 0.05 or 0.5 nmol/side), the NK-3 agonist, senktide (0.005, 0.5 or 1.5 nmol/side), or saline. Two weeks later, the saline-treated rats were assessed in the tail-flick test for phasic pain after infusions of the tachykinin agonists. Tail-flick latencies were recorded following immersion of the tail in 55 degrees C hot water at 10 min intervals for 1 h immediately after intra-VTA infusions of either GR-73632 (0.5 nmol/side), senktide (1.5 nmol/side) or saline. In a second group of rats, the same effects were studied after infusions into the nucleus accumbens (NAS) of GR-73632 (0.005, 0.5 or 1.5 nmol/side), senktide (0.005, 0.5 or 1.5 nmol/side), or saline. In both the VTA and NAS, the NK-1 and the NK-3 agonists caused significant analgesia in the formalin test, although the NK-1 agonist appeared to be more effective. Naltrexone (2.0 mg/kg) pretreatment failed to reverse the analgesic effects in the formalin test induced by intra-VTA infusions of the substance P (SP) analog, DiMe-C7 (3.0 microg/side), GR-73632 (0.5 nmol/side), or senktide (1.5 nmol/side). Neither compound given at either site was effective in the tail-flick test. These findings suggest that SP-dopamine (DA) interactions within the mesolimbic DA system play an important role in the inhibition of tonic pain. Furthermore, they support our earlier ideas that activation of midbrain DA systems by SP might play a role in stress- and/or pain-induced analgesia.

Amphetamine↗

PubMed1996

Opioid receptors in the ventral tegmental area contribute to stress-induced analgesia in the formalin test for tonic pain.

Exposure to stress can induce analgesia in the formalin test for tonic pain. Here, we report that blockade of opioid receptors by bilateral infusions of naltrexone methylbromide (NMB) (0.1 microgram/0.5 microliter/side) in the ventral tegmental area (VTA) in the midbrain can reduce stress-induced analgesia in this test. These findings indicate that endogeneous opioids act in the VTA to mediate stress-induced analgesia in tonic pain.

Analgesia↗

PubMed1993

Intra-VTA infusions of the substance P analogue, DiMe-C7, and intra-accumbens infusions of amphetamine induce analgesia in the formalin test for tonic pain.

Experiments were designed to examine the analgesic effects of SP injected into the ventral tegmental area (VTA). Rats received bilateral intra-VTA infusions of 3.0 micrograms/0.5 microliter/side of the SP analogue, DiMe-C7, or the vehicle, either immediately prior to or 25 min following an injection of 0.05 ml of 2.5% formalin into one hind paw. Formalin-induced pain responses were continuously recorded for 75 min. DiMe-C7 attenuated pain responses for approximately 30 min; the analgesia was more potent and longer-lasting when DiMe-C7 was infused after, rather than prior to, the early pain phase. In another set of experiments, rats were tested in the formalin test immediately following bilateral infusions of amphetamine (1.5 or 2.5 micrograms/0.05 microliter/side) into either the medial prefrontal cortex (mPFC) or the nucleus accumbens septi (NAS). Amphetamine failed to alter pain responses when infused into the mPFC, but both doses attenuated pain responses during 25 min when infused into the NAS. There was no evidence for pain inhibition in the tail-flick test for phasic pain following either intra-VTA DiMe-C7 or intra-NAS amphetamine. The finding that intra-VTA DiMe-C7 and intra-NAS amphetamine produces analgesia in the formalin, but not the tail-flick test, suggests that activation of mesolimbic dopamine (DA) neurons contributes to suppression of tonic pain. Because stressors attenuate tonic pain responses, and are known to cause SP release in the VTA, we speculate that SP-induced activation of midbrain DA systems may mediate a form of pain- or stress-induced pain inhibitory system.

Amphetamine↗