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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptozotocin (STZ)-induced diabetes in the rat has been increasingly used as a model of painful diabetic neuropathy to assess the efficacies of potential analgesic agents. We have established this model, and here we question whether the changes in nocifensive reflex activity, used as a measure of hyperalgesia, are genuinely indicative of peripheral neuropathy or may rather be attributed to the extreme poor health of the animals. For comparison we have examined animals with peripheral neuropathy induced by partial ligation of the sciatic nerve. Diabetic animals were chronically ill, with reduced growth rate, polyuria, diarrhoea, and had enlarged and distended bladders. Indicative of their poor health, diabetic animals showed markedly reduced motor activity. In contrast, following partial sciatic nerve ligation rats showed none of these adverse effects and their motor activity was not different to naive animals. Diabetic animals displayed marked mechanical hyperalgesia, and some thermal hypoalgesia. Morphine and L-baclofen partially reversed established STZ-induced mechanical hyperalgesia, whilst the NK-1 receptor-antagonist RP-67580, the NMDA-antagonists MK801 and ketamine, and the nitric oxide synthase inhibitor L-NAME were without significant effect. Morphine and L-baclofen produced greater reversal of mechanical hyperalgesia following partial nerve ligation, although RP67580 and MK801 showed little or no activity. These data confirm previous findings that STZ-induced diabetes in rats produces long-lasting mechanical, but not thermal hyperalgesia. In our experience this mechanical hyperalgesia is largely resistant to a range of pharmacological tools. However, we feel that the profound ill-health of the animals, together with the poor activity of a range of potential analgesic drugs, must raise questions on the predictive value of these animals as a model for the human condition of chronic diabetic pain seen in patients receiving long-term insulin treatment, as well as ethical concerns on the use of the animals themselves.
Pain 1999 Jun
PMID:Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat. 1043 18

Inflammatory pain involves the sensitization of both primary afferent and spinal cord neurons. To explore the neurochemical changes that contribute to inflammatory pain, we have examined the expression and ligand-induced internalization of the substance P receptor (SPR) in the spinal cord in acute, short-term, and long-term inflammatory pain states. These inflammatory models included unilateral injection of formalin (8-60 min), carrageenan (3 hr), and complete Freund's adjuvant (CFA; 3 d) into the rat hindpaw as well as adjuvant-induced polyarthritis (21 d). In acute inflammatory pain there is ongoing release of substance P (SP) as measured by SPR internalization in lamina I neurons at both 8 and 60 min after formalin injection. Although there is no tonic release of SP in short-term inflammatory pain, at 3 hr after carrageenan injection, SP is released in response to both noxious and non-noxious somatosensory stimulation with SPR internalization being observed in neurons located in both laminae I and III-IV. In long-term inflammatory pain models (CFA and polyarthritis) the same pattern of SP release and SPR activation occurs as is observed in short-term inflammation with the addition that there is a significant upregulation of the SPR in lamina I neurons. These results suggest that SPR internalization might serve as a marker of the contribution of ongoing primary afferent input in acute and persistent pain states. These stereotypical neurochemical changes suggest that there are unique neurochemical signatures for acute, short-term, and long-term inflammatory pain.
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PMID:Spinal substance P receptor expression and internalization in acute, short-term, and long-term inflammatory pain states. 1046 Feb 73

The comorbidity of headache and depression is rarely studied in the elderly. Confounders were seldom controlled in previous studies. From August 1993 to March 1994, we conducted a door-to-door survey to investigate the relationship of headache and depression in a Chinese elderly population (age > or = 65 years old) in two townships of Kinmen, Taiwan. A total of 1421 participants (71%) out of 2003 eligible citizens completed five measurements: a structured headache interview, Geriatric Depression Scale-short form (GDS-S), a survey of chronic medical illness. Cognitive Abilities Screening Instrument and an evaluation of activities of daily living. Headache diagnoses were made according to the criteria of the International Headache Society (IHS), 1988. Depression was defined as a GDS-S score > or = 8. After adjustment for confounding, subjects with more frequent headaches, more severe headaches, diagnoses of IHS migraine or chronic tension-type headaches in the past year, or a lifetime history of any headache including migraine were more likely to be depressed. In addition, the most relevant headache-related predictors of depression were the presence of any reported lifetime headache (odds ratio (OR) = 1.8, P < 0.01) and headache frequency > or = 7 days/month in the past year (OR = 2.0, P = 0.01). This study provided evidence that headache is independently associated with depression in the elderly. A high comorbidity of depression was found in the elderly with IHS migraine or chronic tension-type headaches. Not only the headache profile in the past year but also that in their lifetime was important in predicting current depression in the elderly. 1
Pain 1999 Sep
PMID:Comorbidity of headaches and depression in the elderly. 1048 74

Sciatica is a common pain problem and current pharmacologic therapies have proven inadequate for many patients. The objective of this sham-controlled investigation was to compare a novel non-pharmacologic technique, percutaneous electrical nerve stimulation (PENS), to transcutaneous electrical nerve stimulation (TENS) in the management of the radicular pain associated with sciatica. Sixty-four consenting patients with sciatica due to lumbar disc herniation were treated with PENS, TENS and sham-PENS according to a randomized, single-blinded, cross-over study. All patients had been maintained on a stable oral non-opioid analgesic regimen for at least 6 weeks prior to entering the study. Each treatment modality was administered for a period of 30 min three times per week for 3 weeks, with 1 week 'off' between each modality. Both PENS and TENS treatments were administered using a stimulation frequency of 4 Hz. The pre-treatment assessment included the health status survey short form (SF-36), as well as visual analog scales (VAS) for radicular pain, physical activity and quality of sleep. The pain VAS was also repeated after each treatment session. At the end of each 3-week treatment block, the SF-36 was repeated. After receiving all three treatment modalities, a global assessment questionnaire was completed. Both PENS (42%) and TENS (23%) were significantly more effective than the sham (8%) treatments in decreasing VAS pain scores. The daily oral analgesic requirements were also significantly reduced compared to the pre-treatment values with PENS (P<0.01) and TENS (P<0.05). However, PENS was significantly more effective than TENS (and sham-PENS) in improving physical activity and quality of sleep. The SF-36 evaluation confirmed the superiority of PENS (versus TENS and sham-PENS) with respect to post-treatment functionality. In the overall assessment, 73% of the patients reported that PENS was the most desirable modality (versus 21% for TENS and 6% for sham-PENS). Finally, 71% of the patients stated that they would be willing to pay extra to receive PENS therapy compared to 22% and 3% for TENS and sham-PENS, respectively. In this sham-controlled study, we concluded that PENS was more effective than TENS when administered at a stimulation frequency of 4 Hz in providing short-term pain relief and improved functionality in patients with sciatica.
Pain 1999 Nov
PMID:Percutaneous electrical nerve stimulation: an alternative to TENS in the management of sciatica. 1053 90

The cancer-related event that is most disruptive to the cancer patient's quality of life is pain. To begin to define the mechanisms that give rise to cancer pain, we examined the neurochemical changes that occur in the spinal cord and associated dorsal root ganglia in a murine model of bone cancer. Twenty-one days after intramedullary injection of osteolytic sarcoma cells into the femur, there was extensive bone destruction and invasion of the tumor into the periosteum, similar to that found in patients with osteolytic bone cancer. In the spinal cord, ipsilateral to the cancerous bone, there was a massive astrocyte hypertrophy without neuronal loss, an expression of dynorphin and c-Fos protein in neurons in the deep laminae of the dorsal horn. Additionally, normally non-noxious palpation of the bone with cancer induced behaviors indicative of pain, the internalization of the substance P receptor, and c-Fos expression in lamina I neurons. The alterations in the neurochemistry of the spinal cord and the sensitization of primary afferents were positively correlated with the extent of bone destruction and the growth of the tumor. This "neurochemical signature" of bone cancer pain appears unique when compared to changes that occur in persistent inflammatory or neuropathic pain states. Understanding the mechanisms by which the cancer cells induce this neurochemical reorganization may provide insight into peripheral factors that drive spinal cord plasticity and in the development of more effective treatments for cancer pain.
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PMID:Neurochemical and cellular reorganization of the spinal cord in a murine model of bone cancer pain. 1059 70

Interferon-gamma can facilitate the spinal nociceptive flexor reflex and may elicit neuropathic pain-related behavior in rats and mice. Immunoreactivity for the interferon-gamma receptor (IFN-gamma R) occurs in the superficial layers of the dorsal horn and the lateral spinal nucleus in the rat and mouse spinal cord, as well as in subsets of neurons in the dorsal root ganglia. The aim of the present study was to examine the cellular localization and origin of the IFN-gamma R in the spinal cord. As viewed by confocal microscopy, the immunopositivity for the IFN-gamma R was co-localized with that of the presynaptic marker synaptophysin and with neuronal nitric oxide synthase in the lateral spinal nucleus, whereas only a minor overlap with these molecules was observed in laminae I and II of the dorsal horn. There was no co-localization of the IFN-gamma R with markers for astrocytes and microglial cells. Ultrastructurally, the IFN-gamma R was found predominantly in axon terminals in the lateral spinal nucleus, but at postsynaptic sites in dendrites in laminae I and II. The IFN-gamma R expressed in neurons in dorsal root ganglia was transported in axons both centrally and peripherally. Hemisection of the spinal cord caused no reduction in immunolabelling of the IFN-gamma R in the dorsal horn or the lateral spinal nucleus. Since rhizotomy does not affect the immunolabelling in the lateral spinal nucleus, our observation indicates that the presynaptic receptors in this nucleus are derived from intrinsic neurons. The localization of the IFN-gamma R in the spinal cord differed from that of the AMPA glutamate receptor subunits 2 and 3 and the substance P receptor (NK1). Our results, showing localization of IFN-gamma R to pre- and postsynaptic sites in the dorsal horn and lateral spinal nucleus indicate that IFN-gamma can modulate nociception at the spinal cord level.
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PMID:Interferon-gamma receptors are expressed at synapses in the rat superficial dorsal horn and lateral spinal nucleus. 1064 Jan 90

Mice lacking the gene encoding for substance P and neurokinin A, or the NK-1 receptor, exhibit alterations in behavior to various acute nociceptive stimuli. However, behavioral responses of NK-1 mutant animals have not been well characterized in models of chronic pain. We studied the behavioral responses of NK-1 knockout and wild-type control mice to thermal and mechanical stimuli before and after inducing chronic neuropathic pain by unilateral ligation of the L5 spinal nerve. Mechanical hyperalgesia was evaluated by determining the frequency of withdrawal to von Frey monofilaments applied to the hind paws. Nerve injury-induced hyperalgesia to thermal stimuli was examined by determining responses to radiant heat and cooling stimuli. The contribution of the sympathetic nervous system to mechanical hyperalgesia was evaluated by administering 3 mg/kg phentolamine, an alpha-adrenergic antagonist, subcutaneously. Following spinal nerve injury, withdrawal frequencies to mechanical stimulation increased in wild-type mice within 1 day and persisted during the 9-week observation period, whereas in the knockout mice, withdrawal frequencies did not increase significantly. In contrast, withdrawal latencies to radiant heat decreased up to 2 weeks after nerve injury in both the NK-1 and the wild-type mice. Similarly, the increase in withdrawal frequency to the cooling stimuli following the nerve injury was not different in the NK-1 knockout and wild-type mice. Mechanical hyperalgesia in the wild-type mice was not reversed by systemic administration of phentolamine, suggesting that the pain is not sympathetically maintained. The results indicate that NK-1 receptors contribute to the development of mechanical, but not thermal, hyperalgesia in neuropathic pain.
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PMID:Nerve injury-induced mechanical but not thermal hyperalgesia is attenuated in neurokinin-1 receptor knockout mice. 1073 40

The aim of this investigation was to determine whether murine models of inflammatory, neuropathic and cancer pain are each characterized by a unique set of neurochemical changes in the spinal cord and sensory neurons. All models were generated in C3H/HeJ mice and hyperalgesia and allodynia behaviorally characterized. A variety of neurochemical markers that have been implicated in the generation and maintenance of chronic pain were then examined in spinal cord and primary afferent neurons.Three days after injection of complete Freund's adjuvant into the hindpaw (a model of persistent inflammatory pain) increases in substance P, calcitonin gene-related peptide, protein kinase C gamma, and substance P receptor were observed in the spinal cord. Following sciatic nerve transection or L5 spinal nerve ligation (a model of persistent neuropathic pain) significant decreases in substance P and calcitonin gene-related peptide and increases in galanin and neuropeptide Y were observed in both primary afferent neurons and the spinal cord. In contrast, in a model of cancer pain induced by injection of osteolytic sarcoma cells into the femur, there were no detectable changes in any of these markers in either primary afferent neurons or the spinal cord. However, in this cancer-pain model, changes including massive astrocyte hypertrophy without neuronal loss, increase in the neuronal expression of c-Fos, and increase in the number of dynorphin-immunoreactive neurons were observed in the spinal cord, ipsilateral to the limb with cancer. These results indicate that a unique set of neurochemical changes occur with inflammatory, neuropathic and cancer pain in C3H/HeJ mice and further suggest that cancer induces a unique persistent pain state. Determining whether these neurochemical changes are involved in the generation and maintenance of each type of persistent pain may provide insight into the mechanisms that underlie each of these pain states.
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PMID:Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. 1086 52

We studied the effect of the location of electrical stimulation on the acute analgesic response to percutaneous neuromodulation therapy in patients with nonradiating neck pain. Sixty-eight patients received three different nonpharmacologic modalities, namely "needles only" (neck), local (neck) dermatomal stimulation, and remote (lower back) dermatomal stimulation in a random sequence over the course of an 11-wk study period. All treatments were given for 30 min, 3 times per week for 3 wk, with 1 wk "off" between each modality. The assessment tools included the health status survey short form (SF-36) questionnaire, as well as 10-cm visual analog scales for assessing pain, physical activity, and quality of sleep. The pain visual analog scale was repeated 5-10 min after each treatment session. The daily oral nonopioid analgesic requirements were recorded in the patient diary during the entire study period. At the end of each 3-wk treatment block, the SF-36 questionnaire was repeated. Compared with needles only and remote dermatomal stimulation, local dermatomal stimulation produced a significantly greater decrease in pain (38%+/-17% vs 9%+/- 16% and 13%+/-18%), increase in physical activity (41%+/-21% vs 11% +/-17% and 16%+/-15%), and improvement in the quality of sleep (34% +/-18% vs 7%+/-17% and 10%+/-18%) compared with baseline values (P<0.05). The need for oral analgesic medications was decreased by an average of 6%+/-15%, 37%+/-18%, and 9%+/-13% during the 3-wk treatment period with the needle only, local dermatomal, and remote dermatomal stimulation, respectively. The posttreatment SF-36 test results revealed that all three modalities produced improvements compared with the prestudy scores for both the physical component summary and mental component summary. However, the magnitude of the changes in the physical component summary and mental component summary with local dermatomal stimulation was significantly greater (+7.9 and +3.6, respectively) than needle only (+3.4 and +1.7, respectively) or remote dermatomal stimulation (+3.7 and +1.9, respectively). No side effects were reported at the needle insertion sites. We conclude that electrical stimulation at the specific dermatomal levels corresponding to the local pathology produces greater short-term improvements in pain control, physical activity, and quality of sleep in patients with chronic neck pain.
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PMID:Percutaneous neuromodulation therapy: does the location of electrical stimulation effect the acute analgesic response? 1100 55

Preclinical investigations suggest that the neuropeptide substance P might be involved in the etiopathology of pain, depression, and anxiety. In a recent study, the substance P receptor antagonist MK-869 showed antidepressant and anxiolytic activity in depressed outpatients which was comparable to a standard SSRI. The MK-869 was well tolerated. Although these findings are promising, further studies are necessary to prove the hypothesis that substance P receptor antagonists represent a new class of antidepressants or anxiolytics. Respective studies are currently underway.
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PMID:[Substance P receptor antagonists--a new antidepressive and anxiolytic mechanism?]. 1104 72


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