Pharmacogenomics in pain treatment

Peiró, Ana M.; Planelles, Beatriz; Juhász, Gabriella; Bagdy, György; Libert, Frédéric; Eschalier, Alain; Busserolles, Jérôme; Sperlágh, Beáta; LLerena, Adrián

doi:10.1515/dmpt-2016-0005

Cited by 15 publications

(10 citation statements)

References 120 publications

(127 reference statements)

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“…As an emerging field, pharmacogenetics confronts new challenges such as ensuring its correct standardization and correct translation to routine clinical practice . Pharmacogenetics implementation will require the establishment of stable phenotype‐genotype relationships through controlled clinical trials and cost‐effectiveness studies.…”

Section: Discussionmentioning

confidence: 99%

“…The ABCB1 gene encodes for a P‐glycoprotein transporter, the inhibition of which impacts opiate‐induced analgesia, especially for morphine and oxycodone, and is a major determinant of the pharmacokinetics and pharmacodynamics of several drugs . However, use of pharmacogenetic information has been slow, due in large part to the lack of robust evidence demonstrating clinical utility …”

Section: Introductionmentioning

confidence: 99%

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Genetic Contribution in Low Back Pain: A Prospective Genetic Association Study

et al. 2019

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Objectives Chronic pain is one of the most common reasons individuals seek medical attention. It is a major issue because of the wide interindividual variability in the analgesic response. This might be partly explained by the presence of variants in genes encoding molecules involved in pharmacodynamics and pharmacokinetics. The aim was to analyze opioid effectiveness in chronic low back pain (CLBP) relief after opioid titration, unveiling the impact of pharmacogenetics. Methods The study included 231 opioid‐naïve patients from the Spine Unit; age 63 ± 14 years, 64% female, body mass index 29 ± 6 kg/m2, visual analog scale pain intensity score 73 ± 16 mm. Clinical data were collected at baseline, 3 months after opioid titration, and after 2 to 4 years of follow‐up concerning pain (intensity and relief), quality of life, disability, comorbidities, and drug prescription (opioid dose, rotations, and adverse events). The genotype influence of OPRM1, COMT, UGT2B7, ABCB1, KCNJ6, and CYP3A5*3A in analgesic response was analyzed by reverse‐transcription polymerase chain reaction genotyping. Results Patients with the COMT G472A‐AA genotype (rs4680) and KCNJ6 A1032G‐A allele (rs2070995) CLBP responded differently to opioid titration, with higher pain intensity requiring higher dosing. Furthermore, GG‐ genotypes of A118G (OPRM1, rs1799971) and A854G (UGT2B7, rs776746) influenced the neuropathic component. After opioid titration, CLBP intensity, neuropathic component, low back pain disability, anxiety, and depression significantly decreased, while quality of life improved. Conclusion Single‐nucleotide polymorphisms in genes involved in pain transmission and opioid metabolism might predispose to exaggerated sensitivity and differences in the opioid analgesic effect in patients with CLBP. We encourage clinical trials for their clinical application in chronic pain management.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic Contribution in Low Back Pain: A Prospective Genetic Association Study

et al. 2019

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“…Moreover, several of the genes in the present NGS panel have been implicated in pharmacogenetic modulations of drug effects ( Table 4 ). Possibly the most widely studied gene in analgesic research is OPRM1 because coding for the primary target of opioids ( Peiro et al, 2016 ). Several polymorphisms have been described in OPRM1 , among which the best characterized may be rs1799971 ( OPRM1 118A>G) that leads to an asparagine to aspartate substitution at the extracellular terminal of the receptor protein ( Bond et al, 1998 ).…”

Section: Discussionmentioning

confidence: 99%

“…However, the importance of this variant seems to be comparatively high in patients with an Asian ethnic background, which might be related to the higher allelic frequency as compared to other ethnicities. COMT is a key modulator of dopaminergic neurotransmission and in the signaling response to opioids The Val158Met polymorphism (rs4680) causes an amino acid substitution in the enzyme, which reduced the enzyme active to a forth ( Peiro et al, 2016 ). Carriers of the homozygous Met/Met variant had lower morphine requirements than those with a the wild type COMT ( Rakvag et al, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Development of an AmpliSeqTM Panel for Next-Generation Sequencing of a Set of Genetic Predictors of Persisting Pain

et al. 2018

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Background: Many gene variants modulate the individual perception of pain and possibly also its persistence. The limited selection of single functional variants is increasingly being replaced by analyses of the full coding and regulatory sequences of pain-relevant genes accessible by means of next generation sequencing (NGS).Methods: An NGS panel was created for a set of 77 human genes selected following different lines of evidence supporting their role in persisting pain. To address the role of these candidate genes, we established a sequencing assay based on a custom AmpliSeqTM panel to assess the exomic sequences in 72 subjects of Caucasian ethnicity. To identify the systems biology of the genes, the biological functions associated with these genes were assessed by means of a computational over-representation analysis.Results: Sequencing generated a median of 2.85 ⋅ 106 reads per run with a mean depth close to 200 reads, mean read length of 205 called bases and an average chip loading of 71%. A total of 3,185 genetic variants were called. A computational functional genomics analysis indicated that the proposed NGS gene panel covers biological processes identified previously as characterizing the functional genomics of persisting pain.Conclusion: Results of the NGS assay suggested that the produced nucleotide sequences are comparable to those earned with the classical Sanger sequencing technique. The assay is applicable for small to large-scale experimental setups to target the accessing of information about any nucleotide within the addressed genes in a study cohort.

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“…Two people can have virtually identical lesions and whilst one may recover, the other may develop chronic and intractable pain (Peiro et al, 2016). Genetic components must therefore play a role in human pain vulnerability (Costigan et al, 2009;Zorina-Lichtenwalter et al, 2016).…”

Section: Lost In Translationmentioning

confidence: 99%

K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain

Smith

2020

Front. Cell. Neurosci.

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Sensory abnormalities generated by nerve injury, peripheral neuropathy or disease are often expressed as neuropathic pain. This type of pain is frequently resistant to therapeutic intervention and may be intractable. Numerous studies have revealed the importance of enduring increases in primary afferent excitability and persistent spontaneous activity in the onset and maintenance of peripherally induced neuropathic pain. Some of this activity results from modulation, increased activity and /or expression of voltage-gated Na + channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. K + channels expressed in dorsal root ganglia (DRG) include delayed rectifiers (K v 1.1, 1.2), A-channels (K v 1.4, 3.3, 3.4, 4.1, 4.2, and 4.3), KCNQ or M-channels (K v 7.2, 7.3, 7.4, and 7.5), ATP-sensitive channels (K IR 6.2), Ca 2+-activated K + channels (K Ca 1.1, 2.1, 2.2, 2.3, and 3.1), Na +-activated K + channels (K Ca 4.1 and 4.2) and two pore domain leak channels (K 2p ; TWIK related channels). Function of all K + channel types is reduced via a multiplicity of processes leading to altered expression and/or post-translational modification. This also increases excitability of DRG cell bodies and nociceptive free nerve endings, alters axonal conduction and increases neurotransmitter release from primary afferent terminals in the spinal dorsal horn. Correlation of these cellular changes with behavioral studies provides almost indisputable evidence for K + channel dysfunction in the onset and maintenance of neuropathic pain. This idea is underlined by the observation that selective impairment of just one subtype of DRG K + channel can produce signs of pain in vivo. Whilst it is established that various mediators, including cytokines and growth factors bring about injury-induced changes in DRG function and excitability, evidence presently available points to a seminal role for interleukin 1β (IL-1β) in control of K + channel function. Despite the current state of knowledge, attempts to target K + channels for therapeutic pain management have met with limited success. This situation may change with the advent of personalized medicine. Identification of specific sensory abnormalities and genetic profiling of individual patients may predict therapeutic benefit of K + channel activators.

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Pharmacogenomics in pain treatment

Cited by 15 publications

References 120 publications

Genetic Contribution in Low Back Pain: A Prospective Genetic Association Study

Genetic Contribution in Low Back Pain: A Prospective Genetic Association Study

Development of an AmpliSeqTM Panel for Next-Generation Sequencing of a Set of Genetic Predictors of Persisting Pain

K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain

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