Biomedical subjects

Perry N Fuchs

Publications and source records attributed to Perry N Fuchs.

15 recordsLinked to original sources

PubMed2006

The relationship between basal level of anxiety and the affective response to inflammation.

Pain is a multidimensional experience and is modulated by a number of factors. One such factor that plays a critical role in pain modulation is anxiety. However, the influence of individual differences in anxiety on higher order pain processing in rodents remains unclear. Therefore, the purpose of this study was to identify animals that have baseline levels of high and low anxiety using the elevated plus maze and then measure pain threshold and place escape/avoidance responding (a measure of pain affect) in the animals. As expected, there was a range of baseline behavior in the elevated plus maze that was used to separate animals into high and low anxiety groups. Following carrageenan injection, both groups of animals developed a similar degree of mechanical hypersensitivity and both groups showed similar place escape/avoidance behavior. These findings suggest that individual differences in baseline anxiety levels do not significantly contribute to the development of mechanical sensitivity and do not modulate higher order pain processing related to pain affect and motivation.

Affect↗

PubMed2006

Role of gender norms and group identification on hypothetical and experimental pain tolerance.

Previous research indicates that men typically tolerate more pain in experimental settings than women. One likely explanation for these group differences in pain tolerance is conformity to traditional, gender group social norms (i.e., the ideal man is masculine and tolerates more pain; the ideal woman is feminine and tolerates less pain). According to self-categorization theory, norms guide behavior to the degree that group members adopt the group identity. Therefore, high-identifying men are expected to conform to gender norms and tolerate more pain than high-identifying women who conform to different gender norms as a guide for their behavior. We conducted two studies to investigate whether gender group identification moderates individuals' conformity to pain tolerance and reporting norms. In the first study, participants indicated their gender identification and expected tolerance of a hypothetical painful stimulus. As anticipated, high-identifying men reported significantly greater pain tolerance than high-identifying women. No differences existed between low-identifying men and women. To determine if self-reported pain tolerance in a role-playing scenario corresponds to actual pain tolerance in an experimental setting, the second study examined pain tolerance to a noxious stimulus induced by electrical stimulation of the index finger. The experimental outcome revealed that high-identifying men tolerated more painful stimulation than high-identifying women. Further, high-identifying men tolerated more pain than low-identifying men. These results highlight the influence of social norms on behavior and suggest the need to further explore the role of norms in pain reporting behaviors.

Adaptation, Psychological↗

PubMed2006

GABAA but not GABAB receptors in the rostral anterior cingulate cortex selectively modulate pain-induced escape/avoidance behavior.

The rostral anterior cingulate cortex (rACC) is involved in supraspinal nociceptive processing. ACC lesions relieve persistent pain, but do not affect the patient's ability to localize a noxious stimulus. Since the rACC has a high density of GABA receptors, it is possible that pain processing is influenced by these receptors in the rACC. The present experiments examined the involvement of rat rACC GABA(A) and GABA(B) receptors in regard to sensitivity to mechanical stimulation and escape/avoidance behavior in response to a noxious stimulus following L5 spinal nerve ligation. Rats were or were not afflicted with a neuropathic pain condition by an L5 spinal nerve ligation. rACC microinjection of 10 microg/microl GABA, a GABA(A) agonist (0.001 microg/microl, 0.1 microg/microl, or 0.5 microg/microl muscimol), a GABA(B) agonist (0.1 microg/microl, 1 microg/microl, or 5 microg/microl baclofen), or saline, did not alter mechanical withdrawal thresholds. Importantly, following 10 microg/microl GABA, 0.1 microg/microl, or 0.5 microg/microl muscimol microinjected into the rACC, place escape/avoidance behavior to a noxious mechanical stimulus was attenuated in injured animals. The attenuation was specific to the rACC and was blocked by a preadministered microinjection of the appropriate antagonist(s) into the rACC. In conclusion, microinjection of GABA and higher doses of muscimol did not decrease mechanical hyperalgesia but did attenuate place escape/avoidance behavior that is associated with mechanical stimulation of the ligated paw. These results provide additional support for the role of the rACC in higher order supraspinal processing of noxious events and suggest that rACC GABA(A) receptors significantly contribute to this processing.

Animals↗

PubMed2006

Hyperbaric oxygen treatment decreases inflammation and mechanical hypersensitivity in an animal model of inflammatory pain.

Hyperbaric oxygen therapy has been used to treat a variety of ailments from carbon monoxide poisoning to fibromyalgia. The purpose of this experiment was to explore the effect of hyperbaric oxygen treatment on carrageenan-induced inflammation and pain in rats. Hyperbaric oxygen treatment significantly decreased inflammation and pain following carrageenan injection. Clinically hyperbaric oxygen may be used in situations where NSAIDS are contraindicated or in persistent cases of inflammation.

Animals↗

PubMed2005

Electrical stimulation of the primary somatosensory cortex inhibits spinal dorsal horn neuron activity.

Cortical stimulation has been demonstrated to alleviate certain pain conditions. The aim of this study was to determine the responses of the spinal cord dorsal horn neurons to stimulation of the primary somatosensory cortex (SSC). We hypothesized that direct stimulation of the SSC will inhibit the activity of spinal dorsal horn neurons by activating the descending inhibitory system. Thirty-four wide dynamic range spinal dorsal horn neurons were recorded in response to graded mechanical stimulation (brush, pressure, and pinch) at their respective receptive fields while a stepwise electrical stimulation (300 Hz, 0.1 ms, at 10, 20, and 30 V) was applied in the SSC through a bipolar tungsten electrode. The responses to brush at control, 10 V, 20 V, 30 V, and recovery were 16.0 +/- 2.3, 15.8 +/- 2.2, 14.6 +/- 1.8, 14.8 +/- 2.0, and 17.0 +/- 2.2 spikes/s, respectively. The responses to pressure at control, 10 V, 20 V, 30 V, and recovery were 44.7 +/- 5.5, 37.0 +/- 5.6, 29.5 +/- 4.8, 31.6 +/- 5.2, and 43.2 +/- 5.7 spikes/s, respectively. The responses to pinch at control, 10 V, 20 V, 30 V, and recovery were 58.1 +/- 7.0, 42.9 +/- 5.5, 34.8 +/- 3.9, 34.6 +/- 4.4, and 52.6 +/- 6.0 spikes/s, respectively. Significant decreases of the dorsal horn neuronal responses to pressure and pinch were observed during SSC stimulation. It is concluded that electrical stimulation of the SSC produces transient inhibition of the responses of spinal cord dorsal horn neurons to higher intensity mechanical stimuli without affecting innocuous stimuli.

Action Potentials↗

PubMed2005

Selective regulation of pain affect following activation of the opioid anterior cingulate cortex system.

Morphine and surgical cingulotomy, or transection of the anterior cingulate cortex (ACC), provides relief of chronic pain by selectively decreasing the affective dimension of the condition without altering sensory processing. Clinical reports suggest that morphine might be acting at the level of the ACC to alter the complex experience of pain. Therefore, the purpose of this experiment was to directly examine the functional role of the ACC in processing the aversive nature of pain induced by ligation of the L5 spinal nerve. Systemic administration of low dose morphine produced a selective attenuation of pain affect, as indicated by a decrease in the aversiveness of noxious cutaneous stimulation in nerve-damaged animals, with no alteration of mechanical paw withdrawal threshold. Supraspinally, microinjection of morphine into the ACC produced a selective naloxone reversible reduction in pain affect, as indicated by a decrease in the aversiveness of noxious cutaneous stimulation in nerve-damaged animals, with no alteration of response to mechanical stimulation. These data demonstrate the central role of the ACC opioid system in selectively processing the aversive quality of noxious mechanical stimulation in animals with a persistent pain condition.

Animals↗

PubMed2005

Electrical stimulation of the anterior cingulate cortex reduces responses of rat dorsal horn neurons to mechanical stimuli.

The anterior cingulate cortex (ACC) is involved in the affective and motivational aspect of pain perception. Behavioral studies show a decreased avoidance behavior to noxious stimuli without change in mechanical threshold after stimulation of the ACC. However, as part of the neural circuitry of behavioral reflexes, there is no evidence showing that ACC stimulation alters dorsal horn neuronal responses. We hypothesize that ACC stimulation has two phases: a short-term phase in which stimulation elicits antinociception and a long-term phase that follows stimulation to change the affective response to noxious input. To begin testing this hypothesis, the purpose of this study was to examine the response of spinal cord dorsal horn neurons during stimulation of the ACC. Fifty-eight wide dynamic range spinal cord dorsal horn neurons from adult Sprague-Dawley rats were recorded in response to graded mechanical stimuli (brush, pressure, and pinch) at their respective receptive fields, while simultaneous stepwise electrical stimulations (300 Hz, 0.1 ms, at 10, 20, and 30 V) were applied in the ACC. The responses to brush at control, 10, 20, and 30 V, and recovery were 14.2 +/- 1.4, 12.3 +/- 1.2, 10.9 +/- 1.2, 10.3 +/- 1.1, and 14.1 +/- 1.4 spikes/s, respectively. The responses to pressure at control, 10, 20, and 30 V, and recovery were 39.8 +/- 4.7, 25.6 +/- 3.0, 25.0 +/- 3.0, 21.6 +/- 2.4, and 34.2 +/- 3.7 spikes/s, respectively. The responses to pinch at control, 10, 20, and 30 V, and recovery were 40.7 +/- 3.8, 30.6 +/- 3.1, 27.8 +/- 2.8, 27.2 +/- 3.2, and 37.4 +/- 3.9 spikes/s, respectively. We conclude that electrical stimulation of the ACC induces significant inhibition of the responses of spinal cord dorsal horn neurons to noxious mechanical stimuli. The stimulation-induced inhibition begins to recover as soon as the stimulation is terminated. These results suggest differential short-term and long-term modulatory effects of the ACC stimulation on nociceptive circuits.

Action Potentials↗

PubMed2004

Behavioral evidence for competing motivational drives of nociception and hunger.

Homeostasis, an organisms' tendency to maintain a healthy balance of the physiological state of the body, is necessary for survival. Hunger induces a motivational state to consume food. Recently, pain has been referred to as a homeostatic emotion similar to hunger or thirst in that animals are motivated to respond in a certain way that may increase their chance of survival. Therefore, the purpose of the present experiment was to examine behavior in rodents during two competing homeostatic/motivational drives (i.e., hunger and formalin pain). During the first phase of the formalin test, animals displayed typical responsiveness to the inflammatory condition and completed fewer chains for food reinforcement as compared to the baseline session. However, during the second phase of the formalin test, animals showed decreased nociceptive behavior compared to formalin-injected animals that were not trained in the operant conditioning paradigm. During this phase, the trained animals exhibited maximal responsiveness for food reinforcement. These results demonstrate that the engagement of behaviors reflecting motivational drives to restore homeostasis depends on the intensity or degree of imbalance of the competing drives. More specifically, animals are motivated to attend to one state of imbalance at a time.

Animals↗

PubMed2004

Effect of chronic vincristine treatment on mechanical withdrawal response and pre-pulse inhibition in the rat.

Chemotherapeutic agents are associated with a number of serious side-effects. In addition to the development of peripheral neuropathy, patients often complain of additional symptoms related to attentional mechanisms. Although a great deal of interest is directed towards understanding the mechanisms underlying the development of peripheral neuropathy, there is a paucity of research that has examined the extent of impairment of attention in animals receiving chemotherapeutic agents. Therefore, the purpose of this experiment was to examine attentional mechanisms using the method of pre-pulse inhibition in animals that were chronically treated with vincristine. Although vincristine treated animals developed signs of peripheral neuropathy, there was no associated alteration of pre-pulse inhibition relative to vehicle treated animals. These results highlight the importance of continuing to develop methodology to model symptom burden in patients receiving chemotherapy.

Acoustic Stimulation↗

PubMed2004

Differential effect of anterior cingulate cortex lesion on mechanical hypersensitivity and escape/avoidance behavior in an animal model of neuropathic pain.

Various limbic system structures have been implicated in processing noxious information. One such structure is the anterior cingulate cortex (ACC), a region that is thought to modulate higher order processing of noxious input related to the affective/motivational component of pain. The present experiment examined the involvement of the ACC in higher order pain processing by measuring paw withdrawal threshold and escape/avoidance responses in the L5 spinal nerve ligation model of neuropathic pain before and following electrolytic lesion of the ACC. In the place/escape avoidance paradigm, the afflicted paw is mechanically stimulated when the animal is in the preferred dark area of the chamber and the contralateral paw is stimulated when the animal is in the light area. Escape/avoidance was defined as a shift from the preferred dark area to an increase of time spent in the light area of the chamber. Animals with L5 ligation had significantly lower mechanical paw withdrawal threshold (hypersensitivity) and enhanced escape/avoidance behavior. ACC lesion in animals with L5 ligation did not alter mechanical hypersensitivity, but did significantly decrease escape/avoidance behavior. Anxiety, as measured using the light-enhanced startle paradigm, was not altered by ACC lesion. These results highlight the utility of novel behavioral test paradigms and provide additional support for the role of the ACC in higher order processing of noxious information, suggesting that ACC lesions selectively decrease negative affect associated with neuropathy-induced hypersensitivity.

Afferent Pathways↗

PubMed2003

Decreased L5 spinal nerve ligation nociceptive behavior following L4 spinal nerve transection.

This study used the escape/avoidance paradigm to explore the role of the L4 spinal nerve in L5 ligation nociception. Unlike L5-ligated controls, L5-ligated/L4-transected animals had normal mechanical withdrawal threshold and did not escape/avoid mechanical stimulation of the afflicted paw. The result from the escape/avoidance paradigm, which does not rely on a reflexive withdrawal response, directly supports the hypothesis that the L4 spinal nerve contributes to L5 ligation neuropathic pain.

Animals↗

PubMed2002

Catecholamine depletion by reserpine blocks the anxiolytic actions of ethanol in the rat.

Neurochemical investigations of the anti-anxiety action of ethanol demonstrate that increased dopaminergic, noradrenergic, and serotonergic activity mediates the anxiolytic actions of ethanol. Results of studies with animals and human beings also confirm an involvement of the sympathetic nervous system in the behavioral actions of ethanol. Because enhanced sympathetic activity increases the release of norepinephrine from sympathetic terminals, the interruption of normal sympathetic activity might disrupt the anxiolytic action of ethanol. The present study examined the effect of chemical sympathectomy by reserpine pretreatment on the subsequent anxiolytic action of ethanol. Seventy-one, female, Sprague-Dawley rats were administered reserpine (0 or 5 mg/kg), followed 17-19 h later by ethanol (0, 0.5, or 1.0 g/kg). Animals were then tested in the elevated plus maze. Compared with saline pretreatment, which did not attenuate the anxiolytic actions of a 1.0-g/kg dose of ethanol, reserpine pretreatment completely blocked the anxiolytic action of a 1.0-g/kg dose of ethanol. Reserpine, by itself, did not possess anxiolytic or anxiogenic actions. Because the anxiolytic action of ethanol involves increased catecholamine activity and the depletion of norepinephrine and dopamine from sympathetic nerve terminals by reserpine blocked the anxiolytic action of ethanol, it is concluded that the anxiolytic action of ethanol requires the presence of normal catecholamine activity. We suggest that prostaglandin activity normally evoked by enhanced sympathetic nervous system activity might be involved in the anxiolytic action of ethanol.

Adrenergic Uptake Inhibitors↗

PubMed2001

Enhanced formalin nociceptive responses following L5 nerve ligation in the rat reveals neuropathy-induced inflammatory hyperalgesia.

The development of mechanical and thermal hypersensitivity following peripheral nerve injury is well known and a great deal of research has been directed towards understanding the mechanisms underlying these phenomena. However, there has been very little research examining if hypersensitivity to an inflammatory condition following nerve injury also develops. Therefore, the purpose of the present study was to determine if hypersensitivity to an inflammatory condition produced in the formalin test develops following ligation of the L5 spinal nerve. Male Sprague-Dawley rats received tight ligation of the L5 spinal nerve or were given sham surgery. Following a 14-day recovery period, the threshold to produce a withdrawal response to a mechanical stimulus was measured using von Frey monofilaments and then formalin behavioral responses were measured. Compared to sham animals, L5 ligated animals exhibited significantly lower mechanical paw withdrawal thresholds as well as elevated and prolonged nociceptive responses during the second phase (20-60 min) of the formalin test. These results reveal enhanced inflammatory nociceptive processes following peripheral nerve damage and might provide a useful approach to study underlying neural mechanisms associated with clinical neuropathic pain syndromes.

Animals↗

PubMed2000

Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain.

Tissue injuries, with or without involvement of nerves, may lead to ongoing pain and hyperalgesia to external stimuli. In a subset of patients, the pain is maintained by sympathetic efferent activity (SMP). We investigated if the peripheral administration of the alpha-adrenergic agonist, norepinephrine (NE), in physiologically relevant doses resulted in pain in patients with SMP. To establish the dose of intradermal NE required to induce cutaneous vasoconstriction, NE (1 nM-10 microM, 30 microl) was injected under a laser Doppler probe on the volar forearm of seven normal subjects. A decrease in blood flow was evident at a dose of 10 microM. Twelve patients (five male, seven female) diagnosed to have SMP based on the decrease in pain by a local anesthetic sympathetic blockade (70+/-6%) were enrolled in the study. Pain ratings were obtained continuously for 5 min after intradermal injections of saline and NE (0.1-10 microM) into their hyperalgesic zone and the mirror-image contralateral side. Injections were done during the period of pain relief following a local anesthetic sympathetic blockade. Similar injections were made in eight control subjects. On the affected side of the patients, the two highest concentrations of NE (1 and 10 microM) caused significantly more pain than saline (P<0.05, ANOVA). In contrast, there was no significant pain induced by the NE injections in the unaffected side and in control subjects. Six of nine patients tested reported a marked decrease in pain and hyperalgesia following infusion of phentolamine (1 mg/kg over 10 min). Two of the three patients who did not receive pain relief following phentolamine infusion also did not report pain to the NE injections. We conclude that NE injections produce pain in SMP patients at doses that are at the threshold for producing vasoconstriction. These studies support a role for cutaneous adrenoceptors in the mechanisms of sympathetically maintained pain.

Adrenergic alpha-Agonists↗

PubMed1999

Topical EMLA pre-treatment fails to decrease the pain induced by 1% topical capsaicin.

Topical capsaicin has been reported to be beneficial for the treatment of neurogenic pain. However, due to the burning pain associated with topical capsaicin, many patients discontinue treatment before therapeutic benefits are obtained. This study assessed the efficacy of EMLA (eutectic mixture of 2.5% prilocaine and 2.5% lidocaine) to block pain induced by the topical application of 1% capsaicin. Nine healthy subjects (five males and four females) participated in the study. High dose topical capsaicin (1%) was applied to a 2.5 x 2.5 cm region of both volar forearms for 6 h. One arm was pretreated (for 2 h) and cotreated with EMLA, and the other arm served as vehicle control. Average and peak pain ratings were recorded at 15-min intervals using a 0 (no pain) to 10 (worst possible pain) scale. Average and peak pain ratings were significantly lower at the EMLA site during the first 15-30 min of capsaicin treatment. However, for the remaining 5.5 h of capsaicin treatment, the pain ratings at the EMLA and vehicle sites were not significantly different. The 6 h treatment with high dose topical capsaicin (1%) produced significant desensitization to heat stimuli that was not affected by EMLA treatment. EMLA fails to produce a long lasting attenuation of the pain induced by topical application of 1% capsaicin. These results argue against the use of EMLA to block pain to topical capsaicin during the treatment of neurogenic pain.

Administration, Topical↗