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Biomedical subjects

Timothy J Ness

Publications and source records attributed to Timothy J Ness.

At least 19 recordsLinked to original sources
PubMed2006

Inflammation and enhanced nociceptive responses to bladder distension produced by intravesical zymosan in the rat.

BACKGROUND: Mycotic infections of the bladder produce pain and inflammatory changes. The present study examined the inflammatory and nociceptive effects of the yeast cell wall component, zymosan, when administered into the urinary bladder in order to characterize this form of bladder sensitization. METHODS: Parametric analyses of the time-course (0-48 hr) and concentration (0-2% solutions) variables associated with intravesical zymosan-induced bladder inflammation were performed in female rats. Plasma extravasation of Evan's Blue dye was used as a measure of tissue inflammation. Cardiovascular and visceromotor responses to urinary bladder distension were used as measures of nociception. RESULTS: Zymosan-induced bladder inflammation, as indexed by plasma extravasation of Evan's Blue, was significantly greater in rats treated with either 1 or 2% solutions as compared to either 0.1 or 0.5% zymosan solutions. In time-course studies (1-48 hr post-treatment), 1% zymosan-induced inflammation progressively increased with time following administration, was greatest at 24 hr and began to normalize by 48 hr. In the studies of inflammation-induced changes in nociception, arterial blood pressure (ABP) and visceromotor responses to graded distension of the urinary bladder were significantly increased relative to controls 24 hr after zymosan administration. CONCLUSION: These studies provide important time-course and solution concentration parameters for studies of zymosan-induced inflammation of the bladder and suggest utility of this model for the study of bladder-related pain.

Administration, Intravesical↗
PubMed2006

Characterization of thalamic neuronal responses to urinary bladder distention, including the effect of acute spinal lesions in the rat.

UNLABELLED: Chronic visceral pain has proved to be difficult to treat. This study characterized urinary bladder distention (UBD)-evoked responses of neurons located within the ventrobasal group of the thalamus. Units were also characterized for responses to cutaneous stimuli and colorectal distention (CRD). In addition, the effects of spinal lesions on UBD-evoked responses were examined in a subset of neurons. After a stable response to UBD was established, 3 sequential lesions of the spinal cord at the mid-cervical level were performed, and responses to UBD were determined 1 and 5 minutes later. A majority of the neurons in the ventrobasal group of the thalamus were excited by UBD, demonstrated graded responses to graded distention pressures, and responded to cutaneous stimulation. No correlation between the magnitude of the responses of thalamic neurons to UBD and CRD was found. UBD-evoked thalamic neuronal activity was significantly attenuated after dorsal midline lesions of the spinal cord. The present study is a quantitative description of ventrobasal thalamic neuronal responses to UBD in the rat and provides direct neurophysiologic evidence that nociceptive information from the urinary bladder to the ventrobasal group of the thalamus ascends via a dorsal midline pathway. PERSPECTIVE: The effect of dorsal midline lesions is of profound clinical interest because it points to a potential treatment for urinary bladder pain, such as that which is characteristic of interstitial cystitis. Further research might reveal pharmacologic approaches to modulate this pain pathway and result in novel treatments for interstitial cystitis.

Afferent Pathways↗
PubMed2006

Neonatal urinary bladder inflammation produces adult bladder hypersensitivity.

UNLABELLED: Inflammatory events experienced during early development may permanently alter sensory processing. Because urinary tract infections frequently occur during early development in females and painful bladder disorders have a high female prevalence, the present studies were undertaken to determine whether inflammation of the bladder in female rats could lead to altered sensory processing later in life. Female rat pups were anesthetized and treated as neonates (14th-16th days of life) or as adolescents (28th-30th days of life) with either intravesical zymosan (yeast cell wall component that produces robust inflammation), intravesical normal saline, or only with anesthesia. As adults, rats that had their bladders inflamed as neonates exhibited increased spontaneous micturition frequency and, after reinflammation of the bladder, increased cardiovascular and abdominal muscle contractile responses to urinary bladder distension when compared with controls. Similar effects were not observed in rats which did not experience inflammation of the bladder until adolescence. Evan's blue extravasation, a measure of the magnitude of inflammatory changes, was also greater in rats treated as neonates with intravesical zymosan. Thermal and mechanical hindpaw sensitivity was not altered by bladder inflammation. Altogether, this suggests that neonatal bladder inflammation increases bladder sensitivity and may be a cause of the hypersensitivity of painful bladder syndromes. PERSPECTIVE: The present study observed that bladder inflammation experienced in a neonatal rat led to accentuated responses to urinary bladder distension when tested as adults. This suggests that events experienced during development may permanently sensitize visceral sensory systems and so represent one of the causes of painful bladder disorders.

Abdominal Muscles↗
PubMed2005

Morphine responses and experimental pain: sex differences in side effects and cardiovascular responses but not analgesia.

UNLABELLED: Sex differences in analgesic responses to mu opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to mu opioids, the analgesic effects of intravenous morphine (0.08 mg/kg) were determined in healthy women (n = 61) and men (n = 39) by using 3 experimental pain models, heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both morphine and saline, which occurred on separate days in counterbalanced order. Although morphine produced significant analgesic effects for all pain stimuli, no significant sex differences in morphine analgesia emerged. However, morphine attenuated cardiovascular reactivity to the ischemic pain task in men but not women, and women reported significantly more drug-related adverse effects than men. These findings are in contrast with some recent clinical and experimental results suggesting more robust analgesic response to mu opioids among women compared to men, although the data indicate that sex differences in non-analgesic effects of morphine were present. These results suggest that sex differences in responses to morphine might depend on the pain model and/or drug dose as well as the specific end point assessed. PERSPECTIVE: This study examines morphine responses in women and men by using laboratory pain measures. The results indicate no sex differences in analgesia, but women reported greater side effects, and morphine attenuated cardiovascular responses more strongly among men than women. These results add to the literature regarding sex differences in response to opioids.

Adult↗
PubMed2005

The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans.

Responses to painful stimuli are characterized by tremendous interindividual variability, and genetic factors likely account for some proportion of this variability. However, few studies have identified genetic contributions to experimental pain perception in humans. This experiment investigated whether the A118G single nucleotide polymorphism of the mu-opioid receptor gene ( OPRM1 ) was associated with responses to three different experimental pain modalities in a sample of 167 healthy volunteers (96 female, 71 male). Responses to thermal, mechanical, and ischemic pain were assessed in all subjects, and genotyping of OPRM1 was performed, which revealed that the rare A118G allele occurred in 24 females (25%) and 12 males (17%). Statistical analyses indicated that subjects with a rare allele had significantly higher pressure pain thresholds than those homozygous for the common allele. Also, a sex by genotype interaction emerged for heat pain ratings at 49 degrees C, such that the rare allele was associated with lower pain ratings among men but higher pain ratings among women. These data indicate an association of a common single nucleotide polymorphism of OPRM1 with mechanical pain responses and that this genotype may be associated with heat pain perception in a sex-dependent manner. This study examines the association of the A118G SNP of OPRM1 to experimental pain sensitivity. The results indicate that the rare allele is associated with higher pressure pain thresholds. These results support previous contentions that OPRM1 may be a pain-relevant gene; however, replication of these findings is needed.

Adult↗
PubMed2005

Visceral pain and life quality in persons with spinal cord Injury: a brief report.

BACKGROUND/OBJECTIVE: Few studies have examined the prevalence of visceral pain in persons with spinal cord injury (SCI), and virtually no studies have looked at the relationship between visceral pain and self-reported quality of life. We examined the frequency of reported visceral pain at 5, 10, and 15 years after injury to determine whether the presence of visceral pain is related to quality of life, and to determine to what extent visceral pain should be of concern to clinicians treating patients with SCI. METHODS: Visceral pain and quality of life in persons with SCI were compared from a combined Craig Hospital and National Model SCI Systems database at 5 (N = 33), 10 (N = 132), and 15 (N = 96) years after injury. RESULTS: The rates of visceral pain increased at each measurement (10% at year 5, 22% at year 10, and 32% at year 15); although these numbers reflect cross-sectional data, they do show a clear statistical change. Only a limited true longitudinal sample was available, but at 10 years after injury, individuals who had reported visceral pain at any time reported a significantly lower quality of life than those never experiencing visceral pain, F1,188 = 3.95, P < 0.05. CONCLUSIONS: Although visceral pain may not be as prevalent as the more researched neuropathic and musculoskeletal subtypes of pain, it may account for a higher percentage of people with SCI who report pain than previously recognized. More quantitative and longitudinal research is needed to examine the relationship of visceral pain with overall quality of life and to pursue interventions.

Abdominal Pain↗
PubMed2005

Pelvic pain in women and men: recent findings.

PURPOSE OF REVIEW: All Pubmed-listed articles generated by the search terms 'pelvic' and 'pain' from the year 2004 (plus or minus 6 months) were examined for relevance to pain management therapeutics. An emphasis was given to clinical studies related to chronic pain disorders. RECENT FINDINGS: Use of the descriptive diagnosis 'pelvic pain', traditionally limited to gynecological pains, has now been generalized to include male populations with similar symptom complexes arising from organs of reproduction and other pelvic organ systems such as the gastrointestinal tract and urological structures. Clinical studies have sought to refine or test existing 'standard' therapies for current pain groupings, and have frequently obtained frustrating results because many therapies appear to be effective in only a subset of patients. Notably, the same therapeutics appear to be effective in similar subsets of patients with other protean disorders. SUMMARY: A commonality of symptoms suggests a commonality of pathophysiology, although this has not proved to be globally true. The success of therapeutic options appears to depend upon a stratification of previous pain groupings into overlapping subsets each with their effective treatment. Current studies are still defining these subsets and finding monotherapies to be inadequate for whole populations.

Journal Article↗
PubMed2005

Psychophysical evidence of hypersensitivity in subjects with interstitial cystitis.

PURPOSE: We quantified differences in somatic and visceral sensation in healthy subjects and subjects with interstitial cystitis (IC). MATERIALS AND METHODS: A total of 13 subjects with IC and 13 healthy subjects answered psychological questionnaires and underwent psychophysical testing of thermal and pressure thresholds for sensation as well as the ischemic forearm test of pain tolerance. A subset of subjects also underwent bladder sensory testing with the determination of 3 consecutive cystometrograms. Ratings of intensity and unpleasantness were determined. RESULTS: Subjects with IC were significantly more sensitive to deep tissue measures of sensation related to pressure, ischemia and bladder than healthy subjects. Cutaneous thermal pain measures were similar in the 2 groups. Psychological measures indicated higher reactivity in subjects with IC. CONCLUSIONS: Similar to other visceral pain disorders, such as irritable bowel syndrome, hypersensitivity to somatic stimuli was noted in subjects with IC. This suggests altered central mechanisms in the processing of sensory events from the bladder.

Adult↗
PubMed2005

Menstrual cycle affects bladder pain sensation in subjects with interstitial cystitis.

PURPOSE: Using psychophysical methods we compared the effect of the menstrual cycle on bladder sensation in subjects with the diagnosis of interstitial cystitis (IC) and in controls. MATERIALS AND METHODS: Female participants with normal menstrual cycles, including 7 with IC and 8 healthy controls, were recruited into this study. They completed daily diaries related to bladder pain and other body pain, and tracked daily micturition frequency. In a subset formal psychophysical testing of thermal and ischemic pain was performed at 2 times of the menstrual cycle, corresponding to the luteal and follicular phases. Cystometrograms were performed at the same time. RESULTS: Subjects with IC had higher pain scores and frequency than controls throughout the entire menstrual cycle. Pain scores were highest in the perimenstrual period in subjects with IC and controls. Micturition frequency was highest in the perimenstrual period in subjects with IC. Cystometric evaluation of a first need to void and the evocation of bladder pain demonstrated that lower intravesical volume and pressure were necessary to evoke bladder pain during the follicular period than during the luteal period in subjects with IC, although there was no effect on the first need to void. CONCLUSIONS: These findings are consistent with clinical lore that suggests a perimenstrual flare in pain in subjects with IC. To our knowledge it also demonstrates for the first time a menstrual cycle effect on bladder sensory function in subjects with IC. This suggests a potential role of gonadal hormones on bladder sensory processing and, therefore, a potential role for hormonal modulation as a therapeutic modality in this patient population.

Age Distribution↗
PubMed2004

Sex-related psychological predictors of baseline pain perception and analgesic responses to pentazocine.

Sex differences in pain perception and analgesic responses have garnered increasing attention in recent years. We examined the association of psychological factors to baseline pain perception and pentazocine analgesia among 49 healthy women and 39 men. Subjects completed psychological questionnaires measuring positive and negative affect as well as catastrophizing. Subsequently, responses to experimental pain were assessed before and after double-blind administration of intravenous pentazocine (0.5mg/kg). In correlational analyses, positive affect predicted lower pain sensitivity among men but not women. Negative affect predicted lower baseline pain tolerances among both sexes but predicted poorer analgesia only among men. Catastrophizing was associated with greater pain sensitivity and less analgesia more consistently in men than women. Regression models revealed that positive affect predicted lower overall pain sensitivity and catastrophizing predicted poorer overall analgesic responses among men, while no significant predictors of overall pain or analgesia emerged for women. Moreover, positive affect and catastrophizing were negatively and positively correlated, respectively, with side effects from the medication, but only among men. These findings indicate sex-dependent associations of psychological factors with baseline pain perception, analgesic responses, and medication side effects.

Adult↗
PubMed2004

Experimental pain models reveal no sex differences in pentazocine analgesia in humans.

BACKGROUND: Accumulating evidence suggests that there are sex differences in analgesic responses to opioid agonists. Several studies using an oral surgery pain model have reported more robust analgesia to kappa-agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in kappa-agonist-antagonist effects from studies of experimentally induced pain in humans is lacking. METHODS: Therefore, the analgesic effects of intravenous pentazocine (0.5 mg/kg) were determined in healthy women (n = 41) and men (n = 38) using three experimental pain models: heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both pentazocine and saline, which occurred on separate days in counterbalanced order. RESULTS: Compared with saline, pentazocine produced significant analgesic responses for all pain stimuli. However, no sex differences in pentazocine analgesia emerged. Effect sizes for the sex differences were computed; the magnitude of effects was small, and an equal number of measures showed greater analgesia in men than in women. Also, analgesic responses were not highly correlated across pain modalities, suggesting that different mechanisms may underlie analgesia for disparate types of pain. CONCLUSIONS: These findings indicate significant analgesic responses to pentazocine in both men and women across multiple experimental pain assays, and the absence of sex differences contrasts with previous data from the oral surgery model. The most likely explanation for the discrepancy in results is that of differences in the pain assays. These findings are important because they suggest that sex differences in opioid analgesia may be specific to certain types of pain.

Adolescent↗
PubMed2004

Reliable visceromotor responses are evoked by noxious bladder distention in mice.

PURPOSE: A mouse model of bladder distension (UBD) induced acute visceral nociception was characterized. Murine models of nociception may allow for the investigation of mechanisms of pain and analgesia through the use of genetic models. MATERIALS AND METHODS: Isoflurane anesthetized, spontaneously breathing female C3H/J mice had 24 gauge intravesical catheters transurethrally placed and electrodes implanted in the abdominal musculature and in upper limbs for electromyograms and electrocardiograms. RESULTS: UBD (10 to 80 mm Hg for 20 seconds, phasic air distention) produced reliable, reproducible visceromotor responses (VMRs), that is increased abdominal muscle activity, which were graded with graded UBD. Heart rate and respiratory responses were reliable but not reproducible. Subcutaneous morphine (1 to 4 mg/kg) and intravesical lidocaine (500 microg) produced reversible VMR inhibition. Inflammation produced by intravesical mustard oil (2.5% for 15 minutes with an olive oil control) produced a marked increase in sensitivity to UBD with more robust responses evoked by lower UBD intensities. VMRs were present in decerebrate but not in spinal cord transected mice. Unanesthetized mice had similar responses to UBD but with lower pressure thresholds for VMRs. CONCLUSIONS: These findings suggest the usefulness of the current model system for the study of bladder nociception. In mice UBD evoked VMRs are spinobulbospinal reflexes that are reliable and reproducible, graded in relation to the stimulus, inhibited by analgesics and augmented by the presence of inflammation. Together these data strongly support the use of this model because it may allow the assessment of pharmacogenetic differences among murine strains and the use of transgenic technologies.

Analgesia↗
PubMed2004

Endogenous opioids, blood pressure, and diffuse noxious inhibitory controls: a preliminary study.

A 2003 study suggested that there are age differences in diffuse noxious inhibitory controls (DNIC), a form of endogenous pain inhibition. The present report describes a followup study employing a pharmacological blockade of endogenous opioids, i.e., using naloxone, in a small subset (n=6) of healthy young volunteers to characterize the opioid-dependence of DNIC, as well as DNIC's association with cardiovascular reactivity. Findings suggested that, while opioid blockade enhanced cardiovascular reactivity to cold pain, DNIC was not affected by administering naloxone. Interestingly, greater cardiovascular responses to noxious cold were associated with enhanced DNIC in this small sample. This relationship, which did not appear opioid-dependent, supports previous models integrating cardiovascular activity with the functioning of pain-modulatory systems.

Adult↗
PubMed2003

The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans.

Sex specificity of neural mechanisms modulating nociceptive information has been demonstrated in rodents, and these qualitative sex differences appear to be relevant to analgesia from kappa-opioid receptor agonists, a drug class reported to be clinically effective only in women. Via quantitative trait locus mapping followed by a candidate gene strategy using both mutant mice and pharmacological tools, we now demonstrate that the melanocortin-1 receptor (Mc1r) gene mediates kappa-opioid analgesia in female mice only. This finding suggested that individuals with variants of the human MC1R gene, associated in our species with red hair and fair skin, might also display altered kappa-opioid analgesia. We found that women with two variant MC1R alleles displayed significantly greater analgesia from the kappa-opioid, pentazocine, than all other groups. This study demonstrates an unexpected role for the MC1R gene, verifies that pain modulation in the two sexes involves neurochemically distinct substrates, and represents an example of a direct translation of a pharmacogenetic finding from mouse to human.

Adolescent↗
PubMed2003

Transnasal jet ventilation is a useful adjunct to teach fibreoptic intubation: a preliminary report.

PURPOSE: Fibreoptic intubation (FOI) has become an essential technique in the anesthetic management of patients with difficult airways. Unfortunately, residents may graduate from anesthesiology training programs with insufficient skills in FOI. To enhance resident proficiency at FOI without compromising patient comfort or safety, the technique of transnasal jet ventilation-assisted FOI was developed. This report describes our initial experience with this technique. METHODS: Sixty-four patients scheduled for oromaxillofacial surgery under nasal endotracheal anesthesia were recruited. Twenty-eight residents at all levels of training performed FOI through the patient's right nostril after the induction of general anesthesia and neuromuscular blockade. Oxygenation and ventilation were maintained by a faculty anesthesiologist using a Sanders device to deliver a jet of oxygen through a nasal trumpet placed in the patient's left nostril. The time from induction until completion of the FOI was recorded. Residents were subsequently queried about the educational benefit of the technique using a standardized questionnaire. RESULTS: All residents were able to successfully intubate all patients in this study. Thirteen residents successfully performed intubations on three or more occasions with 70% performing the technique faster on the third trial than on the first. No evidence of hypoxemia, gastric distension, pneumothorax, hemodynamic instability or recall was observed. All respondents to the questionnaire reported that the technique was useful as an educational tool and recommended its use with other residents. CONCLUSION: Transnasal jet ventilation-assisted FOI is a useful method to train residents in FOI while maximizing patient comfort and safety.

Anesthesiology↗
PubMed2003

Individual differences in diffuse noxious inhibitory controls (DNIC): association with clinical variables.

Laboratory pain research has been criticized as being irrelevant to the clinical experience of pain. Previous findings have been inconsistent with some studies suggesting that experimental pain responses may be related to the reported presence or severity of chronic pain, while others report no such associations. However, few of these studies assess a variety of laboratory pain responses, and none has assessed relationships between clinical pain and diffuse noxious inhibitory controls (DNIC) in healthy subjects. We administered questionnaire measures of pain, quality of life, and psychological variables to a sample of healthy adults participating in a laboratory study of age differences in pain responses. DNIC was not related to other laboratory pain responses, psychological variables, or physiological variables measured in the present study. Regression models predicting health-related quality of life (e.g. pain, physical functioning) revealed that age, sex, and DNIC responses explained between 10 and 25% of the variance in these dependent measures. Of the laboratory pain variables, only DNIC was the sole consistent predictor of clinical pain and physical health, with greater DNIC responses related to less pain, better physical functioning, and better self-rated health. In addition, age differences in DNIC appeared to partially mediate age differences in physical functioning. These findings highlight the potential clinical relevance of experimental pain procedures and suggest that DNIC may be the laboratory pain response most closely associated with clinical pain and health-related variables.

Adult↗
PubMed2003

Age-related differences in endogenous pain modulation: a comparison of diffuse noxious inhibitory controls in healthy older and younger adults.

Despite decades of research, hundreds of studies, and a number of recent reviews, the effects of aging on the experience of pain remain poorly understood. Many prior investigators have reported increases in persistent pain conditions and diminished tolerance for certain types of laboratory-induced pain among the elderly. While explanations for these effects often propose senescent decrements in endogenous analgesic systems as a possible contributory mechanism, almost no direct empirical evidence for this hypothesis has yet emerged in human studies. The present investigation was designed to evaluate the existence and nature of these putative age-related differences in endogenous pain inhibition. Groups of healthy younger (n=45, mean age=21.6 years, range=18-25) and older (n=48, mean age=63.1 years, range=55-67) adults participated in a controlled, two-session laboratory assessment of diffuse noxious inhibitory controls (DNIC), a measure of endogenous pain inhibition. In this study, we examined age differences in the effects of concurrent cold pain on ratings of heterotopically presented repetitive noxious thermal stimuli. Interestingly, older adults demonstrated facilitation rather than inhibition of thermal pain during concurrent noxious cold stimulation while younger adults demonstrated some expected DNIC effects (i.e. a reduction in thermal pain ratings during heterotopic stimulation with noxious cold). Collectively, the findings of the present study suggest age-associated decrements in at least one form of endogenous analgesic response. If replicated, such findings of reduced pain-modulatory capacity in the elderly may partially explain age-related differences in the prevalence, severity, and impact of chronic pain.

Adult↗