The inhibition of high-voltage-activated calcium current by activation of MrgC11 involves phospholipase C-dependent mechanisms.

High-voltage-activated (HVA) calcium channels play an important role in synaptic transmission. Activation of Mas-related G-protein-coupled receptor subtype C (MrgC; mouse MrgC11, rat homolog rMrgC) inhibits HVA calcium current (ICa) in small-diameter dorsal root ganglion (DRG) neurons, but the intracellular signaling cascade underlying MrgC agonist-induced inhibition of HVA ICa in native DRG neurons remains unclear. To address this question, we conducted patch-clamp recordings in MrgA3-eGFP-wild-type mice, in which most MrgA3-eGFP(+) DRG neurons co-express MrgC11 and can be identified for recording. We found that the inhibition of HVA ICa by JHU58 (0.001-100nM, a dipeptide, MrgC-selective agonist) was significantly reduced by pretreatment with a phospholipase C (PLC) inhibitor (U73122, 1µM), but not by its inactive analog (U73343) or vehicle. Further, in rats that had undergone spinal nerve injury, pretreatment with intrathecal U73122 nearly abolished the inhibition of mechanical hypersensitivity by intrathecal JHU58. The inhibition of HVA ICa in MrgA3-eGFP(+) neurons by JHU58 (100nM) was partially reduced by pretreatment with a Gßγ blocker (gallein, 100µM). However, applying a depolarizing prepulse and blocking the Gαi and Gαs pathways with pertussis toxin (PTX) (0.5µg/mL) and cholera toxin (CTX) (0.5µg/mL), respectively, had no effect. These findings suggest that activation of MrgC11 may inhibit HVA ICa in mouse DRG neurons through a voltage-independent mechanism that involves activation of the PLC, but not Gαi or Gαs, pathway.

Comparison of intensity-dependent inhibition of spinal wide-dynamic range neurons by dorsal column and peripheral nerve stimulation in a rat model of neuropathic pain.

BACKGROUND: Spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) are thought to reduce pain by activating a sufficient number of large myelinated (Aß) fibres, which in turn initiate spinal segmental mechanisms of analgesia. However, the volume of neuronal activity and how this activity is associated with different treatment targets is unclear under neuropathic pain conditions. METHODS: We sought to delineate the intensity-dependent mechanisms of SCS and PNS analgesia by in vivo extracellular recordings from spinal wide-dynamic range neurons in nerve-injured rats. To mimic therapeutic SCS and PNS, we used bipolar needle electrodes and platinum hook electrodes to stimulate the dorsal column and the tibial nerve, respectively. Compound action potentials were recorded to calibrate the amplitude of conditioning stimulation required to activate A-fibres and thus titrate the volume of activation. RESULTS: Dorsal column stimulation (50 Hz, five intensities) inhibited the windup (a short form of neuronal sensitization) and the C-component response of wide-dynamic range neurons to graded intracutaneous electrical stimuli in an intensity-dependent manner. Tibial nerve stimulation (50 Hz, three intensities) also suppressed the windup in an intensity-dependent fashion but did not affect the acute C-component response. CONCLUSIONS: SCS and PNS may offer similar inhibition of short-term neuronal sensitization. However, only SCS attenuates spinal transmission of acute noxious inputs under neuropathic pain conditions. Our findings begin to differentiate peripheral from spinal-targeted neuromodulation therapies and may help to select the best stimulation target and optimum therapeutic intensity for pain treatment.

Temporal changes in MrgC expression after spinal nerve injury.

Mas-related G-protein-coupled receptor subtype C (MrgC) may play an important role in pain sensation. However, the distribution of MrgC receptors in different subpopulations of rodent dorsal root ganglion (DRG) neurons has not been clearly demonstrated owing to a lack of MrgC-selective antibody. It is also unclear whether peripheral nerve injury induces different time-dependent changes in MrgC expression in injured and uninjured DRG neurons. Here we showed that MrgC immunoreactivity is distributed in both IB4-positive (non-peptidergic) and calcitonin gene-related peptide-positive (peptidergic) DRG neurons in mice and rats. Importantly, the MrgC mRNA level and MrgC immunoreactivity were both decreased in the injured L5 DRG compared to corresponding levels in the contralateral (uninjured) DRG in rats on days 14 and 30 after an L5 spinal nerve ligation. In contrast, mRNA and protein levels of MrgC were increased in the adjacent uninjured L4 DRG. Thus, nerve injury may induce temporal changes in MrgC expression that differ between injured and uninjured DRG neurons. In animal behavior tests, chronic constriction injury of the sciatic nerve induced mechanical pain hypersensitivity in wild-type mice and Mrg-clusterΔ(-/-) mice (Mrg KO). However, the duration of mechanical hypersensitivity was longer in the Mrg KO mice than in their wild-type littermates, indicating that activation of Mrgs may constitute an endogenous mechanism that inhibits the maintenance of neuropathic pain in mice. These findings extend our knowledge about the distribution of MrgC in rodent DRG neurons and the regulation of its expression by nerve injury.

Analgesic properties of loperamide differ following systemic and local administration to rats after spinal nerve injury.

BACKGROUND: The analgesic properties and mechanisms of loperamide hydrochloride, a peripherally acting opioid receptor agonist, in neuropathic pain warrant further investigation. METHODS: We examined the effects of systemic or local administration of loperamide on heat and mechanical hyperalgesia in rats after an L5 spinal nerve ligation (SNL). RESULTS: (1) Systemic loperamide (0.3-10 mg/kg, subcutaneous in the back) dose dependently reversed heat hyperalgesia in SNL rats, but did not produce thermal analgesia. Systemic loperamide (3 mg/kg) did not induce thermal antinociception in naïve rats; (2) systemic loperamide-induced anti-heat hyperalgesia was blocked by pretreatment with intraperitoneal naloxone methiodide (5 mg/kg), but not by intraperitoneal naltrindole (5 mg/kg) or intrathecal naltrexone (20 µg/10 µL); (3) local administration of loperamide (150 µg), but not vehicle, into plantar or dorsal hind paw tissue induced thermal analgesia in SNL rats and thermal antinociception in naïve rats; (4) the analgesic effect of intraplantar loperamide (150 µg/15 µL) in SNL rats at 45 min, but not 10 min, post-injection was blocked by pretreatment with an intraplantar injection of naltrexone (75 µg/10 µL); (5) systemic (3.0 mg/kg) and local (150 µg) loperamide reduced the exaggerated duration of hind paw elevation to noxious pinprick stimuli in SNL rats. Intraplantar injection of loperamide also decreased the frequency of pinprick-evoked response in naïve rats. CONCLUSIONS: These findings suggest that both systemic and local administration of loperamide induce an opioid receptor-dependent inhibition of heat and mechanical hyperalgesia in nerve-injured rats, but that local paw administration of loperamide also induces thermal and mechanical antinociception.

Bipolar spinal cord stimulation attenuates mechanical hypersensitivity at an intensity that activates a small portion of A-fiber afferents in spinal nerve-injured rats.

Spinal cord stimulation (SCS) is used clinically to treat neuropathic pain states, but the precise mechanism by which it attenuates neuropathic pain remains to be established. The profile of afferent fiber activation during SCS and how it may correlate with the efficacy of SCS-induced analgesia are unclear. After subjecting rats to an L5 spinal nerve ligation (SNL), we implanted a miniature quadripolar electrode similar to that used clinically. Our goal was to determine the population and number of afferent fibers retrogradely activated by SCS in SNL rats by recording the antidromic compound action potential (AP) at the sciatic nerve after examining the ability of bipolar epidural SCS to alleviate mechanical hypersensitivity in this model. Notably, we compared the profiles of afferent fiber activation to SCS between SNL rats that exhibited good SCS-induced analgesia (responders) and those that did not (nonresponders). Additionally, we examined how different contact configurations affect the motor threshold (MoT) and compound AP threshold. Results showed that three consecutive days of SCS treatment (50 Hz, 0.2 ms, 30 min, 80-90% of MoT), but not sham stimulation, gradually alleviated mechanical hypersensitivity in SNL rats. The MoT obtained in the animal behavioral study was significantly less than the Aα/ß-threshold of the compound AP determined during electrophysiological recording, suggesting that SCS could attenuate mechanical hypersensitivity with a stimulus intensity that recruits only a small fraction of the A-fiber population in SNL rats. Although both the MoT and compound AP threshold were similar between responders and nonresponders, the size of the compound AP waveform at higher stimulation intensities was larger in the responders, indicating a more efficient activation of the dorsal column structure in responders.

Differential roles of neuronal and endothelial nitric oxide synthases during carrageenan-induced inflammatory hyperalgesia.

The present study investigated the role of neuronal nitric oxide synthase (nNOS) in carrageenan-induced inflammatory pain by combining genomic and pharmacological strategies. Intrathecal injection of the nNOS inhibitor 7-nitroindazole dose-dependently inhibited carrageenan-induced thermal hyperalgesia in both early and late phases in wild-type mice. However in nNOS knockout mice, carrageenan-induced thermal hyperalgesia remained intact in the early phase but was reduced in the late phase. Spinal Ca2+ -dependent nitric oxide synthase (NOS) activity in nNOS knockout mice was significantly lower than that in wild-type mice. Following carrageenan injection, although the spinal Ca2+ -dependent NOS activity in both wild-type and knockout mice increased, the enzyme activity in nNOS knockout mice reached a level similar to that in wild-type mice. On the other hand, no significant difference in spinal Ca2+ -independent NOS activity was noted between wild-type and nNOS knockout mice before and after carrageenan injection. Furthermore, intrathecal administration of the endothelial NOS (eNOS) inhibitor L-N5-(1-iminoethyl)-ornithinein nNOS knockout mice inhibited the thermal hyperalgesia in both early and late phases, though this inhibitor had no effect in wild-type mice. Meanwhile, Western blot showed that eNOS expression in the spinal cord of nNOS knockout mice was up-regulated compared with wild-type mice; immunohistochemical staining showed that the spinal eNOS was mainly distributed in superficial laminae of the dorsal horn. Finally, double staining with confocal analysis showed that the enhanced spinal eNOS was expressed in astrocytes, but not in neurons. Our current results indicate that nNOS plays different roles in the two phases of carrageenan-induced inflammatory pain. In this model, enhanced spinal eNOS appears to compensate for the role of nNOS in nNOS knockout mice.

Intact carrageenan-induced thermal hyperalgesia in mice lacking inducible nitric oxide synthase.

To date, the exact role of inducible nitric oxide synthase (iNOS) in inflammatory pain remains controversial. In the present study, we combined a pharmacological strategy (using a selective iNOS inhibitor) with a genomic strategy (using mice lacking the iNOS gene) to address the function of iNOS in the central mechanism of carrageenan-induced persistent inflammatory pain. In the wild type mice, intrathecal administration of L-N(6)-(1-iminoethyl)-lysine, a selective iNOS inhibitor, significantly inhibited thermal hyperalgesia in the late phase but not in the early phase of carrageenan inflammation. Moreover, iNOS mRNA expression in the lumbar enlargement segments of the spinal cord was dramatically induced at 24 h (late phase) after injection of carrageenan into a hind paw. Interestingly, targeted disruption of iNOS gene did not affect carrageenan-induced thermal hyperalgesia in either the early (2-6 h) or late phase. In the lumbar enlargement segments of iNOS knockout mice, nitric oxide synthase (NOS) enzyme activity remained at a similar level to that of the wild type mice at 24 h after carrageenan injection. We found that intrathecal administration of 7-nitroindazole (a selective neuronal NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (a selective endothelial NOS inhibitor), significantly reduced carrageenan-induced thermal hyperalgesia in both the early phase and the late phase in iNOS knockout mice. We also found that expression of neuronal NOS but not endothelial NOS in the lumbar enlargement segments was significantly increased in iNOS knockout mice compared with wild type mice at 24 h after carrageenan injection. Our results indicate that neuronal NOS might compensate for the function of iNOS in the late phase of carrageenan-induced inflammatory pain in iNOS knockout mice. This suggests that iNOS may be sufficient, but not essential, for the late phase of the carrageenan-induced thermal hyperalgesia.

Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial.

BACKGROUND: Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial. OBJECTIVE: To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN. METHODS: Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication. RESULTS: Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02). CONCLUSIONS: Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.

The role of mu-opioid receptors in inflammatory hyperalgesia and alpha 2-adrenoceptor-mediated antihyperalgesia.

The purpose of the present study was to investigate the role of mu-opioid receptor in inflammatory hyperalgesia in intact and in spinalized animals and the interaction between mu-opioid and alpha2-adrenergic receptor in acute pain and inflammatory hyperalgesia. Behavioral responses to mechanical and heat stimuli were studied in mu-opioid receptor knockout mice and wildtype control mice. Thermal nociception was evaluated by measuring paw withdrawal latencies to radiant heat applied to the hindpaws. Mechanical nociception was measured by von Frey monofilament applications to the hindpaws. Intraplantar carrageenan-induced (1 mg/40 microl) mechanical and heat hyperalgesia were compared in micro-opioid knockout and wildtype mice. The effect of systemically administered alpha2-adrenergic receptor agonist dexmedetomidine (1-10 microg/kg) was evaluated on mechanical and thermal withdrawal responses under normal and inflammatory state in knockout and wildtype mice. The role of micro-opioid receptor in descending modulation of nociception was studied by assessing mechanical and heat withdrawal responses before and after mid-thoracic spinalization. Withdrawal responses to radiant heat and von Frey monofilaments were similar in mu-opioid knockout and wildtype mice before and after the carrageenan induced hindpaw inflammation. Also, antinociceptive effects of dexmedetomidine in thermal and mechanical nociceptive tests were similar before carrageenan induced hindpaw inflammation. However, the potency of dexmedetomidine was significantly reduced in carrageenan-induced mechanical hyperalgesia in mu-opioid knockout mice compared to the wildtype control mice. Thermal and mechanical withdrawal responses were similar between mu-opioid knockout and wildtype mice before and after mid-thoracic spinalization. Our observations indicate that the mu-opioid receptors do not play an important role in alpha2-adrenergic receptor agonist-mediated acute antinociception. In addition, micro-opioid receptors are not tonically involved in the modulation of inflammation-induced mechanical and thermal hyperalgesia, and the supraspinal control of spinal reflexes. However, in the presence of inflammation, mu-opioid receptors play an important role in the antihyperalgesic actions of an alpha2-adrenergic receptor agonist.

Consumption of soy diet before nerve injury preempts the development of neuropathic pain in rats.

BACKGROUND: A previous report using a partial sciatic nerve ligation (PSL) model for neuropathic pain in rats demonstrated that consumption of soy-containing diets preoperatively and postoperatively suppressed development of mechanical and heat allodynia, as well as hyperalgesia. The current study examined whether dietary soy suppresses these neuropathic sensory disorders when consumed either before or after PSL injury. METHODS: Male Wistar rats were grouped into seven different feeding regimens. These rats were fed SOY (RMH-1000, PMI Feeds, St. Louis, MO), a diet containing 85% soy protein since weaning, and were then switched to noSOY (Bio-Serv Co., Frenchtown, NJ), a diet devoid of soy at certain time points before PSL injury (14, 7, 1 days, or 15 and 0 h). Postoperatively, these rats were fed SOY or noSOY diets. Levels of mechanical and heat allodynia and hyperalgesia were determined preoperatively and 3, 8, and 14 days after PSL injury. RESULTS: Compared with groups fed preoperative noSOY, consumption of SOY before PSL injury significantly blunted postoperative levels of allodynia and hyperalgesia. Administering the SOY diet both before and after PSL injury provided no additional suppression of neuropathic pain. No pain suppression was noted in rats fed a noSOY diet preoperatively and SOY diet after PSL injury. Switching from SOY to noSOY feeding within 15 h of PSL injury was sufficient to allow for the full development of allodynia and hyperalgesia. CONCLUSIONS: Consumption of a soy-containing diet suppressed the development of neuropathic pain after PSL injury. The pain-suppressing properties of dietary soy were the result of a preemptive effect (i.e., when consumed preoperatively), but not a palliative effect (i.e., when consumed postoperatively). This effect of soy-containing diets appears to be short-lived, since switching to a noSOY diet 15 h before ligation abrogated the suppressive effect of soy.

Sensory processing in the deep spinal dorsal horn of neurokinin-1 receptor knockout mice.

BACKGROUND: The neurokinin-1 receptor and its primary ligand, substance P, are widely recognized as contributing to the spinal processing of nociceptive stimuli, yet the specific function of the neurokinin-1 receptor remains unclear. METHODS: To better clarify these functions, the authors examined the neurophysiologic responses of L4-L5 neurons in the deep dorsal horn to acute mechanical, thermal, and electrical stimuli in knockout and wild-type mice. In addition, the capacity of knockout and wild-type mice to show wind-up to repeated C-fiber stimuli and to show sensitization after cutaneous mustard oil was assessed. RESULTS: A total of 68 nociceptive neurons (35 in knockout, 33 in wild type) in laminae III-V were studied. No differences in the acute responses of neurons in knockout and wild-type mice to graded mechanical, thermal, or electrical stimuli or in the acute responses to mustard oil were observed. However, wind-up to repeated electrical stimulation at C-fiber intensity was significantly attenuated in the knockout mice compared with wild type controls. In addition, mustard oil-induced mechanical hypersensitivity was significantly reduced in the knockout mice. CONCLUSIONS: These results indicate that neurokinin-1 receptors do not play a significant role in the responses of nociceptive neurons in the deep spinal dorsal horn to acute noxious mechanical, thermal, electrical, or chemical stimuli. On the other hand, neurokinin-1 receptors are critical for the central hyperexcitability that is observed in these neurons with repeated C-fiber inputs and to the central sensitization induced by topical mustard oil application.

Soy-containing diet suppresses chronic neuropathic sensory disorders in rats.

UNLABELLED: Partial sciatic nerve ligation (PSL) in rodents produces chronic neuropathic sensory disorders resembling neuropathic pain in humans. We previously reported that levels of allodynia and hyperalgesia after PSL injury were markedly attenuated by consumption of soy-containing diets. Here we aimed to show that dietary effect on pain behavior is not specific to a certain laboratory. For this purpose, experiments were conducted in a different laboratory (Baltimore rather than Jerusalem) and a different rat strain (Wistar rather than Sabra), with additional and different testing methods (radiant heat from a lamp rather than a CO(2) laser). Rats were fed two soy-free diets and a soy-containing one for 28 days. The sensitivity of rats to nonnoxious and noxious stimuli was determined before PSL injury, and levels of neuropathic sensory disorders were determined after it. We found that consuming the soy-containing diet prevented development of tactile and heat allodynia, but not mechanical hyperalgesia. This dietary effect was not correlated with calorie intake and weight gain or dietary concentration of fat and carbohydrates. We conclude that, regardless of experimental site, diet markedly affects chronic neuropathic sensory disorders in rats and should be standardized in animal models of pain. IMPLICATIONS: Levels of chronic sensory disorders in a rat model of allodynia and hyperalgesia after partial sciatic nerve ligation depend on the consumption of a soy-containing diet. Further studies are needed to determine the role of diet in humans with chronic pain.

Heat, but not mechanical hyperalgesia, following adrenergic injections in normal human skin.

The development of adrenergic sensitivity in nociceptors has been suggested as a mechanism of neuropathic pain. We sought to determine if nociceptors in the skin of normal subjects exhibit adrenergic sensitivity. We investigated the effects of intradermal administration of norepinephrine, phenylephrine, and brimonidine on heat pain sensitivity. Norepinephrine and phenylephrine (in concentrations ranging from 0.1 to 10 microM by factors of 10), brimonidine (at 0.01-1 microM), and saline were injected (30 microl volume) in a random, double-blind manner to different sites on the volar surface of the forearm in ten subjects. Before and after the injections, heat testing was performed with a non-contact laser thermal stimulator. Heat pain threshold was measured by means of a 'Marstock' technique in which subjects pressed a reaction time key when they perceived that a slowly increasing heat stimulus (1 degrees C/s ramp from a 36 degrees C base) was painful. In addition, the subjects used magnitude estimation techniques to rate the intensity of pain to a suprathreshold heat stimulus (47 degrees C, 2 s). Mechanical testing was done using 200-microm diameter probes attached to calibrated weights that provided forces over the range of 16-512 mN. The intradermal injections of norepinephrine, phenylephrine and brimonidine produced little evoked pain. However, a dose-dependant decrease in heat pain threshold, but not mechanical pain threshold, was observed. At the highest drug dose injected, all three adrenergic compounds produced a significant decrease in heat pain threshold compared to the saline injection. A significant increase in response to the suprathreshold heat stimulus was also found. One possible explanation for this apparent heat hyperalgesia is that the decrease in perfusion due to the localized vasoconstriction may alter the heat response. However, in control studies we found that the non-adrenergic vasoconstrictors, angiotensin II and vasopressin did not produce heat hyperalgesia at doses that produced comparable decreases in blood flow. In addition, occlusion of blood flow with a blood pressure cuff did not lead to heat hyperalgesia. Thus, the heat hyperalgesia observed with the adrenergic agonists is not due to a decrease in perfusion associated with the injection. These results indicate that alpha(1)- and alpha(2)-adrenoceptor-mediated mechanisms may play a role in sensitization of nociceptors to heat stimuli in normal skin.

Age-related thermoregulatory differences during core cooling in humans.

The current study assessed sympathetic neuronal and vasomotor responses, total body oxygen consumption, and sensory thermal perception to identify thermoregulatory differences in younger and older human subjects during core cooling. Cold fluid (40 ml/kg, 4 degrees C) was given intravenously over 30 min to decrease core temperature (Tc) in eight younger (age 18-23) and eight older (age 55-71) individuals. Compared with younger subjects, the older subjects had significantly lower Tc thresholds for vasoconstriction (35.5 +/- 0.3 vs. 36.2 +/- 0.2 degrees C, P = 0.03), heat production (35.2 +/- 0.4 vs. 35.9 +/- 0.1 degrees C, P = 0.04), and plasma norepinephrine (NE) responses (35.0 vs. 36.0 degrees C, P < 0.05). Despite a lower Tc nadir during cooling, the maximum intensities of the vasoconstriction (P = 0.03) and heat production (P = 0.006) responses were less in the older compared with the younger subjects, whereas subjective thermal comfort scores were similar. Plasma NE concentrations increased fourfold in the younger but only twofold in the older subjects at maximal Tc cooling. The vasomotor response for a given change in plasma NE concentration was decreased in the older group (P = 0.01). In summary, aging is associated with 1) a decreased Tc threshold and maximum response intensity for vasoconstriction, total body oxygen consumption, and NE release, 2) decreased vasomotor responsiveness to NE, and 3) decreased subjective sensory thermal perception.

Lumbar sympathetic block for sympathetically maintained pain: changes in cutaneous temperatures and pain perception.

UNLABELLED: Lumbar sympathetic block (LSB) is used in the management of sympathetically maintained pain states. We characterized cutaneous temperature changes over the lower extremities after LSB. Additionally, we examined the effects of iohexol, a radio-opaque contrast medium, on temperature changes and pain relief. After institutional review board approval and written, informed consent, 28 LSBs were studied in 17 patients. Iohexol or normal saline was injected in a randomized, double-blinded fashion before bupivacaine. Lower extremity cutaneous temperatures were measured. Pain, allodynia, interference with daily function, and perceived pain relief were reported in a subset of 15 LSBs for 1 wk after the block. The distal lower extremity ipsilateral to the LSB had the greatest magnitude (8.7 degrees +/- 0.8 degrees C) and rate (1.1 degrees +/- 0.2 degrees C/min) of temperature change. The great toe temperature was within 3 degrees C of core temperature within 35 min after LSB. There were no differences in temperature change between the groups. The iohexol group had greater relief of pain until the morning of the first postblock day (P = 0.002) and longer perceived relief of pain (P = 0.01). The maximum temperature of the great toe correlated with allodynia relief (P = 0.0007). Thus clinicians should expect ipsilateral toe temperatures to increase to within approximately 3 degrees C of core temperature. Iohexol does not alter the efficacy of LSB and may improve relief of symptoms. The magnitude of temperature change may predict relief of allodynia. IMPLICATIONS: Cutaneous toe temperatures approaching core temperature provide a useful monitor of lumbar sympathetic block and may predict relief of sympathetically maintained pain. Iohexol will not compromise temperature changes or pain relief.

Psychiatric symptoms and distress differ between patients with postherpetic neuralgia and peripheral vestibular disease.

OBJECTIVE: No previous studies have investigated the psychiatric characteristics of patients with postherpetic neuralgia (PHN). Similarly, no studies have been performed on patients with different chronic somatic symptoms due to a defined medical disease to compare the characteristics of psychiatric morbidity associated with each etiology. METHODS: After completing the subscales of the Symptom Checklist 90-R, a psychiatrist administered the Diagnostic Interview Schedule to all subjects. The psychiatric comorbidity in 35 patients with pain due to PHN was compared with a control group of 34 patients with the nonpainful aversive symptom of vertigo due to a peripheral vestibular disorder that caused unilateral hypofunction. RESULTS: PHN patients had significantly more symptoms of major depression and somatization disorder. No significant differences were found between groups for psychiatric diagnoses. Patients with PHN reported significantly less acutely distressing somatic symptoms. CONCLUSION: These results suggest that the psychiatric symptoms of patients with PHN are distinct from nonspecific acute distress and may be related to the experience of suffering from chronic neuropathic pain. Patients with PHN may not meet criteria for a psychiatric diagnosis, but their psychiatric comorbidity places them at substantial risk for increased pain, suicidal ideation, sustained disability, and the numerous complications of excessive medical evaluation and treatment. Patients with PHN should be evaluated specifically for psychiatric symptoms to reduce potential negative consequences through appropriate treatment.