Peter Kamerman

University of the Witwatersrand | wits · Brain Function Research Group (BFRG)

Adversity in childhood is robustly associated with persistent pain in adulthood. Neuro-immune interactions are a candidate mechanistic link between childhood adversity and persistent pain, given that both childhood adversity and persistent pain are associated with neural and immune upregulation in adulthood. As such, we aimed to clarify whether imm...

Background: Peripheral abdominal nerve blocks contribute to multimodal postoperative analgesia that enhances early recovery after caesarean sections. The transversus abdominis plane (TAP) block is an established technique that offers somatic abdominal analgesia. The erector spinae plane (ESP) block is a novel fascial plane block that may offer addi...

Background The Sensation and Pain Rating Scale (SPARS) allows rating of non-painful as well as painful percepts. While it performs well in the experimental context, its clinical utility is untested. This prospective, repeated-measures study mixed qualitative and quantitative methods to examine the utility and performance of the SPARS in a clinical...

SARS-COV-2, the viral pathogen that resulted in the COVID-19 pandemic, was first identified by the World Health Organization (WHO) on 31 December 2019. Efforts to curb the spread of this virus, as well as the effects of viral infections and resulting complications thereof, have placed immense strain on healthcare systems throughout the world. In So...

HIV-associated sensory neuropathy (HIV-SN) affects 14-38% of HIV+ individuals stable on therapy with no neurotoxic drugs. Polymorphisms in CAMKK2, P2X7R and P2X4R associated with altered risk of HIV-SN in Indonesian and South African patients. The role of CaMKK2 in neuronal repair makes this an attractive candidate, but a direct role for any protei...

HIV stigma may influence physical activity in people living with HIV (PLWH) and chronic pain. We prospectively examined the relationship between stigma, activity and chronic pain in a convenience sample of PLWH initiating antiretroviral therapy in an inner-city clinic in Johannesburg, South Africa. Participants wore accelerometers to measure daily...

Background: Despite effective antiretroviral therapy (ART), milder forms of HIV-associated neurocognitive disorders remain prevalent and are characterized by neuroinflammation, synaptic dysfunction, and neuronal loss. Methods: We explore associations between neurocognitive impairment in HIV+ Indonesians and 17 polymorphisms in adjacent genes inv...

We review the known physiological mechanisms underpinning all of pain processing, sleep regulation, and pharmacology of analgesics prescribed for chronic pain. In particular, we describe how commonly prescribed analgesics act in sleep-wake neural pathways, with potential unintended impact on sleep and/or wake function. Sleep disruption, whether pai...

The advent of effective antiretroviral therapy (ART) has decreased the prevalence and severity of HIV-associated neurocognitive disorders (HAND), but milder forms of HAND remain despite optimal treatment. Neuronal injury and loss due to inflammation may mediate HAND. P2X7R encodes purinergic P2X receptor 7 which influences neuroinflammatory pathway...

Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. It affected 57% of South African patients whose antiretroviral therapy (ART) included stavudine and was influenced by genotypes of the P2X-block (P2X7R, P2X4R and CAMKK2). We investigate associations between HIV-SN and P2X-blo...

Pain affects over half of the people living with HIV/AIDS (LWHA), and pharmacological treatment has limited efficacy. Preliminary evidence supports nonpharmacological interventions. We previously piloted a multimodal intervention in amaXhosa women LWHA and chronic pain in South Africa with improvements seen in all outcomes, in both intervention and...

Background: Neuropathic pain affects 7-10% of people, but responds poorly to pharmacotherapy, indicating a need for better treatments. Mechanistic research on neuropathic pain frequently uses human surrogate models of the secondary hyperalgesia that is a common feature of neuropathic pain. Experimentally induced secondary hyperalgesia has been man...

Background: The frequency of pain is reported to be high in people living with HIV (PLWH), but valid comparisons between PLWH and HIV-negative cohorts are rare. We investigated whether HIV infection influenced frequency and characteristics of pain in adults undergoing voluntary testing for HIV. Methods: Participants were recruited from a HIV volunt...

Background The pain threshold is traditionally conceptualised as a boundary that lies between painful and non-painful events, suggesting a reasonably stable relationship between stimulus and response. In two previous experiments, participants received laser stimuli of various intensities and rated each stimulus on the Sensation and Pain Rating Scal...

In experiments on pain, participants are frequently exposed to nonpainful and painful stimuli; however, the conventional pain-rating scales lack a nonpainful range and a clear point of transition from nonpainful to painful events. The Sensation and Pain Rating Scale (SPARS) assesses the full stimulus intensity range, extending from no sensation (ra...

Background The use of the HIV antiretroviral drug stavudine (d4T), a thymidine analogue, is associated with the development of mitochondrial toxicities such as sensory neuropathy (SN). Genetic variation in genes relating to d4T transport and metabolism, as well as genetic variation in the thymidine synthesis pathway, could influence occurrence of d...

Associations of 26 SNPs with SN in multivariable models, calculated in gPLINK using logistic regression taking into account age and height. (DOCX)

Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here we analyze time-dependent changes in estimated tr...

The SAMRC brought key stakeholders representing all nine faculties of health sciences at South African universities together on 08 February 2017 at the SAMRC Medicina Campus, Cape Town, to explore opportunities for conducting local research and clinical trials of medicinal cannabis and cannabinoids to inform local policy-making. The workshop identi...

HIV-associated sensory neuropathy (HIV-SN) is a common, and frequently painful complication of HIV, but factors that determine the presence of pain are unresolved. We investigated: (i) if psychological factors associated with painful (n = 125) versus non-painful HIV-SN (n = 72), and (ii) if pain and psychological factors affected quality of life (Q...

Polymorphisms in P2X4R and CAMKK2 associate with susceptibility to HIV-associated sensory neuropathy (HIV-SN) - a condition likely mediated by TNFα. As single nucleotide polymorphisms (SNPs) and haplotypes of CAMKK2, and a neighbouring gene P2X4R, mark susceptibility to HIV-SN in South Africans living with HIV, we examined the relationship between...

Objective: HIV-associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving anti-retroviral therapy (ART), even though neurotoxic anti-retroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesise that chemokines produced locally in the s...

Despite the use of safer antiretroviral medications, the rate of HIV-associated sensory neuropathy (HIV-SN), the most common neurological complication of HIV, remains high. This condition is often painful and has a negative effect on quality of life. Up to 90% of those with HIV-SN experience pain for which there is no effective analgesic treatment....

The effect of sleep deprivation on pain sensitivity has typically been studied using total and partial sleep deprivation protocols. These protocols do not mimic the fragmented pattern of sleep disruption usually observed in individuals with clinical pain conditions. Therefore, we conducted a controlled experiment to investigate the effect of sleep...

Background: Studies on relationships between sex, ethnicity, and pain have largely emanated from the United States and Europe. We compared cold (CPT) and pressure pain tolerance (PPT) in male and female South Africans of African and European ancestry and assessed whether psychosocial factors (including pain beliefs) predicted differences in pain t...

HIV-associated sensory peripheral neuropathy (HIV-SN) afflicts approximately 50% of patients on antiretroviral therapy, and is associated with significant neuropathic pain. Simple accurate diagnostic instruments are required for clinical research and daily practice in both high- and low-resource setting. A 4-item clinical tool (CHANT: Clinical HIV-...

Age of participants stratified by diagnosis. In both cohorts of Johannesburg and London, there was no statistically significant increase in age (years) from no-neuropathy (CHANT-ve), to neuropathy (CHANT +ve), and to neuropathic pain (CHANT+ve, BFP+ve, DN4-I+ve) (Kruskal-Wallis followed by Dunn’s post-hoc analysis). (TIF)

Sensitivity and specificity analysis of measurand items employed within the HIV-PINS (Pain in Neuropathy Study–HIV) dataset. The triumvirate HIV-PINS diagnostic criteria of clinical findings, QST (Quantitative Sensory Testing) abnormalities, and IENFD (Intraepidermal Nerve Fiber Density) results were used as gold-standard. Clinical items with high...

Partial Eta-squared values of measurand items employed within the HIV-PINS (Pain in Neuropathy Study–HIV) dataset. The four clinical items with high sensitivity and specificity i.e. feet numbness, feet pain, reduction in ankle reflex and great toe vibration that were selected to construct CHANT (Clinical HIV-associated Neuropathy Tool) also carried...

NRS (Numerical Rating Scale), DAPOS (Depression, Anxiety, and Positive Outlook Scale), BPI (Brief Pain Inventory), and ISI (Insomnia Severity Index) scores in London cohort. NRS, DAPOS, BPI, and ISI showed observable progressively increasing trend from no-neuropathy (CHANT-ve), neuropathy (CHANT+ve), neuropathy with bilateral feet pain (CHANT+ve, B...

Frequency of Interpreter Requirement among the study patients in Phase-III (Johannesburg). More than half of the patients required interpreters for the items of ‘tingling’, ‘numbness’, and ‘pins and needles’; this reminds the importance of devising tools that have better comprehensibility for their enhanced utility in field settings where English i...

Female:Male (F:M) ratio stratified by diagnosis. F:M ratio was up to 13 times higher in Johannesburg compared to London. F:M ratio was comparable among those with no neuropathy (CHANT-ve), neuropathy (CHANT+ve), and neuropathic pain (CHANT+ve, BFP+ve, DN4-I+ve). (TIF)

Case definition for HIV-SN used by BPNS, UENS, and TCSS. (PDF)

Height of participants stratified by diagnosis. In both cohorts of Johannesburg and London, there was no statistically significant difference in height among cases with no-neuropathy (CHANT-ve), neuropathy (CHANT +ve), and neuropathic pain (CHANT+ve, BFP+ve, DN4-I+ve) (Kruskal-Wallis followed by Dunn’s post-hoc analysis). (TIF)

Waist:Hip ratio of participants stratified by gender and diagnosis. Among females, CHANT+ve neuropathy and neuropathic pain (NeP) (CHANT+ve, BFP+ve, DN4-I+ve) cases had no statistically significant difference in W:H ratio compared to CHANT-ve. Among males, there was no statistically significant difference in W:H ratio between CHANT+ve neuropathy, N...

BMI (Body Mass Index) of participants stratified by diagnosis. In both cohorts of Johannesburg and London, there was no statistically significant difference in BMI among cases with no-neuropathy (CHANT-ve), neuropathy (CHANT +ve), and neuropathic pain (CHANT+ve, BFP+ve, DN4-I+ve) (Kruskal-Wallis followed by Dunn’s post-hoc analysis). (TIF)

Comparison of DN4-I (Interview part of Douleur Neuropathique 4 Questions) scores among all, no neuropathy (CHANT-), neuropathy (CHANT+), neuropathy with bilateral feet pain (CHANT+, BFP+), and neuropathic pain (CHANT+, BFP+, DN4-I+) patients in London cohort Phase II CHANT internal validation study. There was statistically significant difference be...

London CHANT validation study: Inter-median comparison of age, height, and other sociodemographic variables. (PDF)

Instruction on how to perform CHANT. (PDF)

Standards Checklist for the CHANT Prototype (COSMIN). (PDF)

London CHANT validation study. Outcomes of NPSI to describe the 9 (CHANT+ve, BFP) patients who showed varied characteristics and severity on all 12 questions. Permanent spontaneous feet pain (question #4 of NPSI) was present among 3 of the 9 (33.33%), while 6/9 (66.67%) stated to have 6–10 episodes of feet pain attacks during the previous 24 hours...

Pain burden is high in people living with HIV (PLWH), but the effect of this pain on functionality is equivocal. Resilience, the ability to cope with adversity, may promote adaptation to pain, so we hypothesised that higher resilience would correlate with less pain-related impairment of activity. We recruited 197 black South African PLWH, 99 with c...

Correlations between resilience and activity.

Pain characteristics of the chronic pain group. Pain severity and pain interference as recorded from the BPI.

Validation of the resilience scales.

Comparison of activity between groups with and without chronic pain.

Associations between activity (measured objectively with actigraphy) and pain interference and intensity (measured subjectively using the BPI walking, EQ5D mobility and BPI worst pain intensity questions). No patients reported having moderate or severe difficulties with mobility on the EQ5D.

The redefinition of neuropathic pain as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system,” which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system o...

HIV-associated sensory neuropathy (HIV-SN) is a common complication of HIV and remains highly prevalent even with modern HIV management strategies, causing debilitating pain in millions globally. We review HIV-SN diagnosis and management. We suggest most HIV-SN cases are easily recognized using clinical screening tools, with physician assessment an...

HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs) in a cluster of three genes that affect inflammati...

HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection, and often is painful. Tumour necrosis factor (TNF)-α is implicated in neuropathic pain, but associations between neuropathic pain and polymorphisms in the TNFA gene have not been identified. The "TNF block" is a region of high linkage disequilibrium w...

ABOUTThis GitHub repository contains all the files required to generate the application (and supporting documents) the International Association for the Study of Pain (IASP) and the International Association of Hospice and Palliative Care (IAHPC) made to the 21st meeting of the WHO Expert Committee on Selection and Use of Essential Medicines (2017)...

ABOUTThis GitHub repository contains all the files required to generate the application (and supporting documents) the International Association for the Study of Pain (IASP) and the International Association of Hospice and Palliative Care (IAHPC) made to the 21st meeting of the WHO Expert Committee on Selection and Use of Essential Medicines (2017)...

For genetic research to contribute more fully to furthering our knowledge of neuropathic pain, we require an agreed, valid, and feasible approach to phenotyping, to allow collaboration and replication in samples of sufficient size. Results from genetic studies on neuropathic pain have been inconsistent and have met with replication difficulties, in...

Background. HIV-associated sensory neuropathy (HIV-SN) is a common and frequently painful complication of HIV infection and its treatment. However, few data exist describing the frequency, type and dosage of pain medications patients are receiving in the clinic setting to manage the painful symptoms of HIV-SN. Objective. To report on analgesic pres...

Unlabelled: We conducted a randomized, double-blind, placebo-controlled, crossover study at a single center in South Africa, to ascertain whether amitriptyline is an effective analgesic for painful HIV-associated sensory neuropathy of moderate to severe intensity in: i) antiretroviral drug naive individuals, and ii) antiretroviral drug users. 124...

New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG)...

Palliative care, including effective management of cancer pain, is recognised under international law as a human right. Pain management can and should be delivered from the time of cancer diagnosis. This care is inexpensive, safe and effective and can be delivered in a variety of settings including hospitals, outpatient clinics, residential hospice...

Cross-sectional studies report that pain in ambulatory HIV-infected individuals is frequent and often undermanaged. Expanding access to HIV treatment in developing countries means that infected individuals are living longer, but there is a dearth of pain-directed studies from developing countries that describe the progression of pain and its treatm...

HIV-associated sensory neuropathy (HIV-SN) is a common neurological complication of HIV infection. The TNF block is a region within the central MHC that contains many immunoregulatory genes. Polymorphisms and haplotypes of the TNF block have been associated with increased risk of HIV-SN in Asians and whites. Here we investigated genetic association...

The terminology used to describe neuropathic pain appears to be conserved across languages, which facilitates the translation of validated neuropathic pain screening tools into other languages. However, this assumption has not been assessed in an African language. Therefore we investigated the terminology used by 54 patients whose native language w...

Introduction: Animal and in vitro models of HIV-associated sensory neuropathy suggest an inflammatory etiology. Previous genetic association studies of HIV-SN have been in small Caucasian or Asian cohorts. We assessed cytokine single nucleotide polymorphisms (SNPs) in a Black Southern African cohort. Method: 342 black HIV-positive Southern Afric...

Haplotypes spanning the tumor necrosis factor (TNF) gene block in the central major histocompatibility complex were defined in a Southern African population using 31 single-nucleotide polymorphisms. Twenty haplotypes accounted for 91.8% of the cohort. The haplotypes matched those described previously in Caucasian and Asian populations, supporting t...

KCNS1 and GCH1 were investigated for their association with pain intensity in black Southern Africans with HIV-associated sensory neuropathy. Previously associated single nucleotide polymorphisms (SNPs) were supplemented with population specific tagSNPs. No SNPs in KCNS1 individually associated with pain intensity.However, several haplotypes of pop...

SUMMARY Painful HIV-associated sensory neuropathy (HIV-SN) is an early recognized neurological complication of HIV. The introduction of effective HIV treatments saw increased rates of HIV-SN, with some antiretrovirals (notably stavudine) being neurotoxic. Although neurotoxic antiretrovirals are being phased out, the available data suggest that inci...

Sensory neuropathy (SN) is a common and difficult to manage cause of chronic pain in HIV. Recent recommendations for earlier HIV treatment and avoidance of neurotoxic antiretroviral drugs (such as stavudine) have led to optimism that HIV-SN rates may decline. We present several reasons as to why HIV-SN is likely to remain prevalent, despite improve...

Neuropathic pain (NeuP) is challenging to diagnose and manage, despite ongoing improved understanding of the underlying mechanisms. Many patients do not respond satisfactorily to existing treatments. There are no published guidelines for diagnosis or management of NeuP in South Africa. A multidisciplinary expert panel critically reviewed available...

Neuropathic pain (NeuP) is challenging to diagnose and manage, despite ongoing improved understanding of the underlying mechanisms. Many patients do not respond satisfactorily to existing treatments. There are no published guidelines for diagnosis or management of NeuP in South Africa. A multidisciplinary expert panel critically reviewed available...

HIV-associated sensory neuropathy (HIV-SN) is a frequent neurological complication of HIV infection and its treatment with some antiretroviral drugs. We review the pathogenesis of the viral- and drug-induced causes of the neuropathy, and its primary symptom, pain, based on evidence from in vivo and in vitro models of HIV-SN. Viral coat proteins med...

HIV-associated sensory neuropathy (HIV-SN) remains a common neurological complication of HIV infection despite the introduction of effective antiretroviral therapies. Exposure to neurotoxic antiretroviral drugs and increasing age have consistently been identified as risk factors for HIV-SN, while comorbid conditions with underlying predisposition t...

We analyzed GTP cyclohydrolase 1 in symptomatic HIV-associated sensory neuropathy in Southern Africans including a "pain-protective" 3-SNP haplotype and 6 SNPs, analyzed individually and in a 6-SNP haplotype. The "pain-protective" 3-SNP haplotype and a 6-SNP haplotype containing these alleles associated with a reduced risk of pain. Another 3-SNP ha...

We investigated the prevalence and intensity of pain, factors associated with having pain, and analgesic medications employed in a population consisting predominantly of Black African and female human immunodeficiency virus (HIV)-positive individuals attending outpatient clinics in a rural (n = 125; 79% female; 100% Black African) and a metropolita...

SUMMARY Sub-Saharan Africa is the region worst affected by the HIV epidemic and we estimate that at least 10 million HIV-positive individuals in sub-Saharan Africa live with significant pain related to their disease. Until recently there was a lack of studies specifically addressing pain related to HIV infection in sub-Saharan Africa, which limited...

The objective of this study was to determine whether viral double-stranded RNA analog, polyinosinic:polycytidylic acid (Poly-I:C), is pyrogenic in rats when administered subcutaneously, thus determining whether rats can serve as an experimental model to investigate the regulation of local and systemic inflammatory responses to a Toll-like receptor(...

Using implanted temperature loggers, we measured core body temperature in nine western grey kangaroos every 5 min for 24 to 98 days in spring and summer. Body temperature was highest at night and decreased rapidly early in the morning, reaching a nadir at 10:00 h, after ambient temperature and solar radiation had begun to increase. On hotter days,...

HIV-associated sensory neuropathy (HIV-SN) is a frequent complication of both HIV and neurotoxic antiretroviral medications such as stavudine. To determine the prevalence, risk factors, and clinical characteristics of symptomatic HIV-SN in a Black South African cohort of patients exposed to stavudine. HIV-positive Black South Africans (n=395) who h...

We investigated the effects of intraperitoneal injections of a combination of two cyclo-oxygenase inhibitors, ibuprofen and paracetamol, with a weak opiate, codeine, on nociception in Sprague Dawley rats. Administration of paracetamol (11, 44, and 88 mg/kg), ibuprofen (8.75, 35, and 140 mg/kg) or codeine (0.44, 1.75, and 3.5mg/kg) alone caused a do...

Sensory neuropathy (SN) is common in patients with HIV. Hepatitis C (HCV) coinfection is often cited as an HIV-SN risk factor, but data to support this are lacking. This collaboration aimed to examine the association between HCV serostatus and SN risk among ambulatory HIV-positive patients. Patients with HIV were assessed in cross-sectional studies...